Method for identifying the quantitative cellular composition in a biological sample

ABSTRACT

The present invention provides an epigenetic haemogram, also referred to as an epigenetic blood cell count that identifies the quantitative, comprehensive picture of cellular composition in a biological sample, wherein advantageously a normalization standard is used. The normalization standard is a nucleic acid molecule comprising at least one marker-region being specific for each of the blood cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies on said molecule and/or a natural blood cell sample of known composition. Furthermore, the present invention relates to a kit and the use of a kit for performing the epigenetic assessment of comprehensive, quantitative cellular composition of a biological sample. The biological sample is derived from e.g. a mammalian body fluid, including peripheral, capillary or venous blood samples or subfractions thereof, such as peripheral blood mononuclear cells or peripheral blood monocytes, or a tissue sample, organ sample, or from frozen, dried, embedded, stored or fresh body fluids or tissue samples.

The present invention provides an epigenetic haemogram, also referred to as an epigenetic blood cell count that identifies the quantitative, comprehensive picture of cellular composition in a biological sample, wherein advantageously a normalization standard is used. The normalization standard is a nucleic acid molecule comprising at least one marker-region being specific for each of the blood and/or immune cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies on said molecule and/or a natural blood cell sample of known composition. Furthermore, the present invention relates to a kit and the use of a kit for performing the epigenetic assessment of comprehensive, quantitative cellular composition of a biological sample. The biological sample is derived from e.g. a mammalian body fluid, including peripheral, capillary or venous blood samples or subfractions thereof, such as peripheral blood mononuclear cells or peripheral blood monocytes, or a tissue sample, organ sample, or from frozen, dried, embedded, stored or fresh body fluids or tissue samples.

BACKGROUND OF THE INVENTION

A “blood count”, “complete blood count”, or “blood cell profile” commonly designates a set of tests to determine the number, ratio and appearances of blood cells and/or their cellular subgroups (e.g., neutrophils, eosinophils, basophils, CD19 or CD3 cells, and their subgroups, such as CD3⁺CD4⁺ and/or CD3⁺/CD8⁺ cells). Such a blood count is used in clinical diagnostics as a broad screening test for disorders or a determination of the general health status of an individual. In general, a “blood count” includes assays directed at hematocrit, quantification of hemoglobin, total blood cells, and red blood cell index (e.g. mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution).

White blood cells (also referred to as leukocytes) are part of the cellular immune system (we explicitly define all immune cells, including B-cells as cellular immune system) and play a key role in defending an mammals from pathological effects caused either by foreign organisms (in particular for example: viruses, bacteria, parasites, etc.), but also from aberrations of diseased self-cells, such as tumor cells. In addition, immune cells are themselves subject to diseases, either as primary (congenital) immune diseases, such as the IPEX syndrome or as secondary (acquired) immune diseases, such as for example AIDS, HIV. In the former, the immune system itself is impaired, whereas in the latter external factors (such as virus infections, radiation, chemotherapies or environmental factors) lead to a weakening of the immune system. Several types of leukocytes exist and they either derive from the myeloid lineage—e.g. neutrophil, eosinophil and basophil granulocytes, mast cells and macrophages—or derive from the lymphoid lineage including all lymphocyte subpopulations—such as for example T-cells, B-cells, NK cells. Since the composition of the immune system, and its cellular members, has been subjected to many analyses, aberrations of this normal immune cell count (or ratio) can be recognized easily, is used diagnostically, and may be used for clinical decision-making. Thus, the ratio and count of these cells are regularly analyzed in clinical settings—both as routine diagnostic or analytical tool as well as in clinical research or trials—in order to detect any abnormalities or apparent changes that may be caused by a disease or a disease treatment or other internal or external factors. For example, blood counts are used to diagnose the onset/occurrence of leuko- or lymphopenias or leuko- or lymphocytosis, such as granulocytosis. Furthermore, blood counts are taken to monitor the treatment success of all diseases that result from, cause or whose treatment may result in changes of the overall or specific leuko- or lymphocyte counts. For example, for diagnosing or monitoring infections, anemia; leukemia or the effects of chemotherapies, a so-called “differential” whole blood count is used in order to analyze and identify immune cells and subpopulations thereof. In some primary and secondary immune disorders, this procedure may be the only available diagnostic tool. The differential blood count includes assays directed at a quantification of total white blood cells, neutrophil granulocytes, lymphocytes, monocytes, eosinophil granulocytes, and basophil granulocytes.

Routinely, for soluble cells, i.e., mainly blood but also solubilized tissues or body fluids such a specific immune cell profile is measured by flow cytometry, or by immunohistochemistry (IHC) for solid tissues. Both technologies work on the basis of protein epitopes exposed on cell membranes that are specific for each subtype of cell subpopulation. Recently, research focused on the biological role of leukocyte subpopulations, and this results in a strong demand for clinical as well as for research applications allowing to identifying such populations.

Technically, in routine diagnostics, hematocrit, hemoglobin as well as total white blood counts are determined by an automatic cell counter based on light detection and electrical impedance. A differential white blood count, including neutrophil, eosinophil, basophil granulocytes, monocytes and mast cells are determined either via manual microscopic counting or automatic counting of blood smears.

Additional methods, allowing for the detection of T cell populations are MHC multimetric analyses, the Cytokine-Capture Assay, individual T cell detections (ELISPOT-Assay) or the merely qualitative detection and localization of immune cells (immunohistochemical analyses). Like flow cytometry, these assays are based on a detection of proteins; no specific expression level-independent markers are used. It is noteworthy that all of these assays as well as all assays based on the detection of mRNA, vary from cell to cell. This is because even cells that are undoubtedly positive for a certain protein present time wise varying amounts of protein. Hence, a threshold for “positivity” has to be determined for each and every protein marker depending on the affinity and unspecific binding properties of the given antibody as well as on the average amount of surface expression of the target protein.

Even though almost all cells in an individual contain the exact same complement/composition of DNA code, higher organisms must impose and maintain different patterns of gene expression in the various types of tissue. Most gene regulation is transitory, depending on the current state of the cell and changes in external stimuli. Persistent regulation, on the other hand, is a primary role of epigenetics—heritable regulatory patterns that do not alter the basic genetic coding of the DNA. DNA methylation is the archetypical form of epigenetic regulation; it serves as the stable memory for cells and performs a crucial role in maintaining the long-term identity of various cell types. Recently, other forms of epigenetic regulation were discovered. In addition to the “fifth base” 5-methylcytosine (mC), a sixth (5-hydroxymethylcytosine, hmC), seventh (5-formylcytosine, fC) and eighth (5-carboxycytosine, cC) can be found (Michael J. Booth et al. Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution Science 18 May 2012, Vol. 336 no. 6083 pp. 934-937). The primary target of mentioned DNA modifications is the two-nucleotide sequence Cytosine-Guanine (a ‘CpG site’); within this context cytosine (C) can undergo a simple chemical modification to become formylated, methylated, hydroxymethylated, or carboxylated. In the human genome, the CG sequence is much rarer than expected, except in certain relatively dense clusters called ‘CpG islands’. CpG islands are frequently associated with gene promoters, and it has been estimated that more than half of the human genes have CpG islands (Antequera and Bird, Proc Natl Acad Sci USA 90: 11995-9, 1993).

For one of the recently described modification of cytosine, 5-hydroxymethylation, the utility of oxidative bisulfite sequencing to map and quantify 5hmC at CpG islands was shown (Michael J. Booth et al. Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution Science 18 May 2012, Vol. 336 no. 6083 pp. 934-937).

In the context of the present invention, the term “bisulfite convertible chromatin” shall mean a chromatin structure (e.g. a sufficiently opened structure) that allows bisulfite to chemically modify cytosines. Consequently, the term “DNA bisulfite convertibility” relates to the extent of cytosine bases in said chromatin and/or the respective nucleic acid that is part of said chromatin, that can be (or have been) converted using a bisulfite treatment. The term also relates to the extent of cytosine bases in a reference nucleic acid (such as a plasmid) that can be (or have been) converted using a bisulfite treatment. In turn, the term “non-bisulfite convertible chromatin” or “non-bisulfite convertible nucleic acid” relates to the extent of cytosine bases that cannot be (or could not been) converted using a bisulfite treatment.

As mentioned above, recently three new cytosine modifications were discovered. Therefore, it is expected that future scientific findings will lead to a more precise interpretation of epigenetic patterns of bisulfite convertibility described in the past. These past result of cytosine modification encompass bisulfite convertible (non-methylated, non-modified) and non-convertible (methylated, modified) cytosine. Both termini need to be reinterpreted, as described. According to the novel scientific findings (i) non-bisulfite convertible cytosine encompasses 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC), and (ii) bisulfite convertible cytosine encompasses 5-formylcytosine (fC), 5-carboxycytosine (cC) as well as non-modified cytosine.

Additionally, earlier inventions are based on (i) the ratio of bisulfite convertible cytosine to whole amount of chromatin (cell-type independent, 100% bisulfite convertible DNA locus) or (ii) on the ratio of bisulfite convertible cytosine (fC, cC, non-modified cytosine) to non-bisulfite convertible cytosine (hmC and mC). These ratios are used to characterize cell type, cell differentiation, cell stage as well as pathological cell stages. Therefore, new techniques will result in novel, more specific ratios and might supplement current cell specific, cell state specific as well as pathological patterns of epigenetic modifications and therefore, define potential novel biomarkers. Novel ratios to be discovered as biomarkers can be defined as:

Biomarker Ratio=a/b

a=Σ(C and/or mC and/or hmC and/or fC and/or cC) b=Σ(C and/or mC and/or hmC and/or fC and/or cC), whereby a and b differs from each other by one to four kinds of modifications. Discovery of novel DNA modifications will certainly broaden this enumeration.

For the purpose of the present application, epigenetic modifications in the DNA sequence is referred to by the terminology of (i) bisulfite convertible cytosine (5-formylcytosine, (fC) and/or 5-carboxycytosine (cC)) and (ii) non-bisulfite convertible cytosine ((including 5-methylcytosine (mC), 5-hydroxymethylcytosine, (hmC)). As both kinds of methylation, mC and hmC are not bisulfite convertible it is not possible to distinguish between these two. Likewise, IC, cC as well as non-modified cytosine are bisulfite convertible and can also not be distinguished from each other as well.

Furthermore, apart from the modifications of DNA also histones undergo posttranslational modifications that alter their interaction with DNA and nuclear proteins. Modifications include methylation, acetylation, phosphorylation, ubiquitination, sumoylation, citrullination, and ADP-ribosylation. The core of the histones H2A, H2B, and H3 can also be modified. Histone modifications act in diverse biological processes such as gene regulation, DNA repair, chromosome condensation (mitosis) and spermatogenesis (meiosis). Also for these modifications a specific pattern of modification is specific for different cell types, cell stages, differentiation status and such a pattern can be analyzed for bisulfite convertibility or similar methods in order to identify certain cells and cell stages. The present invention also encompasses a use of these modifications.

It is expected that further variants of DNA modifications will be discovered in future. Each type of modification will be either bisulfite-convertible or not. These novel modifications can also be used as biomarker readout. Additionally, it is expected that novel methods for bisulfite modification will be established, resulting in a different set of convertible and non-convertible DNA.

The variety of indications for which reporting of the cellular immune status is clinically or analytically helpful is very large. For almost every disease the cellular immune status is either directly relevant or—such as in cancer—becomes relevant due to the impact of drugs that may cause secondary immunological disorders and aberrations. This broad significance of the overall immune status in diseases settings results in a significant demand for methods to measure these parameters, i.e., the leukocyte subtypes and subpopulations.

The current way of addressing this demand is by flow cytometric and immunohistochemical methods, which are well-established and have been developed into high throughput systems for hospital use, are standard procedures in reference laboratories and are, for more simple applications, made available for practitioners. However, certain problems and requirements limit the applicability of flow cytometry and immunohistochemistry.

a) For flow cytometry, cells need to be intact. This means that the blood sample has to be measured in a “fresh” state, any delay in measurement may lead to deviation of results. As a rule of thumb, samples should be measured within 8 hours, since after that time frame granulocytes (one main cellular fraction in the blood) begin to disintegrate. As an alternative to fresh handling, it is possible to cryopreserve blood samples, but there are significant issues associated with respect to performance and reproducibility. As a consequence, flow cytometry in clinical routine is avoided and many potentially meaningful analyzes are omitted, whereas in clinical trials, where immune markers are prime biomarker candidates for treatment predictions, are often left out, or if required by regulations extra facilities need to be set up. b) Antigen expression is not a digital (on-off), but an analog (low, medium, high) process. Therefore, thresholds defining positive versus negative signals must be determined. For certain markers, this is unproblematic, for others thresholds are very difficult and imprecise. c) For flow cytometry, it also poses problems that many cell types are not simply identified by a surface (cluster of differentiation—CD) molecule, but some cell types are characterized by intra- or extracellular soluble proteins, e.g. transcription factors or cytokines. Current markers for Tfh, Th1, Th2 cells, and Tregs belong to this category of cell types—the application of fully standardized procedures is even more difficult. This is because the cell-type specific markers need to be captured in order to be associated to the cell. d) Furthermore, flow cytometry is dependent on the solubility of the analyzed substrate (cell suspensions). With respect to this, tissue cells may be solubilized by enzymatic digestion, but this often leads to the loss of their surface molecules—rendering the CD markers, as prime targets for flow cytometric analysis useless. e) Often, neither surface- nor intra- or extracellular markers are 100% cell-type specific. “Leaky” expression of certain gene products has been reported (Wiezcorek et al., Cancer Res. 2009 Jan. 15; 69(2):599-608), rendering the quantification somewhat imprecise. f) Since immunohistochemistry is based on the same principle as flow cytometry, specificity problems overlap. However, the main problem with this technology is that it is considered only semiquantitative. In particular, a particular problem is that an overall cell counting is not feasible due to the presence of various different cell layers, which are difficult to distinguish and count correctly.

As far as aspect e) is concerned, the inventors have previously published a publication proving that flow cytometry detects expressed surface epitopes, but it cannot distinguish between cell-type specific epitope expression and cell-type independent induction of epitope expressions as well as it cannot detect specific-cells that currently not express or less express certain surface markers. In vitro stimulation of CD4⁺CD25⁺CD45RA⁺ T cells, for example, leads to a high expression level of FOXP3 whereby the FOXP3 gene is still methylated and therefore inactivated (Baron et al., Epigenetics. 2006 January-March; 1(1):55-60). Additionally, for in vitro differentiated Th17 cells no demethylation of IL-17A promotor was observed despite high levels of IL-17A transcripts (Janson P. C. J. et al. Profiling of CD4+ T cells with epigenetic immune lineage analysis. The Journal of Immunology. 2010, 92-102). On the other side it is disclosed that methylation is connected with marker expression (Hamerman, Page, Pullen. Distinct methylation states of the CD8β gene in peripheral T cells and Intraepithelial Lymphocytes. The Journal of Immunology 1997, P1240-1246; Janson P. C. J. et al. Profiling of CD4+ T cells with epigenetic immune lineage analysis. The Journal of Immunology. 2010. 92-102; Melvin et al. Hypomethylation in IFN-Gamma Gen correlates with expression of IFN-G, including CD8 cells., Eur J Immunol. 1995 February; 25(2):426-30; Landolfi M M et al. CD2⁻CD4⁻CD8⁻ lymph node T lymphocytes in MRL lpr/lpr mice are derived from a CD2⁺CD4⁺CD8⁺ thymic precursor J Immunol. 1993 Jul. 15; 151(2):1086-96; and Carbone A M et al. Demethylation in CD8 suggests that CD4+ derives from CD8⁺ cells. Role of methylation pattern during cell development. Science. 1988 Nov. 25; 242(4882):1174-6).

In view of the above mentioned demands in both clinical diagnostics and pharmaceutical research, a new method to provide a precise and comprehensive quantification of a variety of cell types in a sample is desired, in order to establish a more precise and thus markedly improved haemogram. Further objects and advantages will become apparent to the person of skill upon reading the present disclosure, and particularly the examples below.

In a first aspect thereof, this object is solved by the present invention by a method for producing an epigenetic haemogram, comprising the steps of epigenetically detecting blood cells in a biological sample, and quantifying said blood cells as detected using a normalization standard, wherein said normalization standard is a nucleic acid molecule comprising at least one marker-region being specific for each of the blood cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies on said molecule and/or a natural blood cell sample of known composition.

Key and basis of the present invention is the use of a variety of different cell-type specific bisulfite-convertible DNA marker. These markers are employed for the identification and quantification of a single blood and immune cell types.

In principle, it was previously shown how a quantification of cell types and blood cell counting based on known epigenetic procedures is performed ((Wiezcorek et al., Cancer Res. 2009 Jan. 15; 69(2):599-608, Sehouli et al. Epigenetics: 2011 February; 6(2):236-46.). In brief, either a cell type specifically modified gene region is specifically (amplified and) counted and hence quantitated along with the opposite species of the cell type specific gene region. To provide for an independent quantification, these two measurements arc then put into relation to provide the percentile part of the cell type in the given (blood) sample:

Copy number of bisulfite convertible DNA of cell-type specific genomic region/(copy number of bisulfite convertible DNA of cell-type specific genomic region)+(Copy number of non-bisulfate convertible DNA of cell-type specific genomic region)=% cell type

Alternatively, the number of copies of bisulfite convertible DNA of a cell-type specific gene region is measured and divided by the copy number of bisulfite-convertible DNA of a cell-type non-specific gene region in the given sample. The latter can be determined by measuring all DNA copies using a completely bisulfite-convertible, cell-unspecific gene region or a region that is known to be uniformly bisulfite-unconvertible or bisulfite-convertible in all cell types.

Copy number of bisulfite convertible DNA of cell-type specific genomic region/Copy number of a bisulfite convertible DNA of cell-type unspecific genomic region=% cell type

Hence, when a single specific bisulfite-convertible genomic marker is known, the previously established system allows the relative (percentile (%)) quantification of any one cell type in a given sample. For this, any given standardization of copy numbers or copy equivalents can be used. The resulting percentile share of the cell type in question correlates with the share of cells measured with a different method. Here, “correlating” means that—according to Spearman correlation—the lowest share measured by the epigenetic technology corresponds to the lowest share measured by—for example—flow cytometry. Such system has been shown to be very stable, technically robust and reliable. Therefore, whenever there is a highly cell-specific bisulfite convertible DNA marker achieved, in theory it should be possible to make an accurate and precise determination of the amount of those cells that own the specific bisulfite convertible genomic marker region.

It is known that the efficiency and performance of Real time (RT-)PCR systems differ depending on the RT-PCR components, including primers, probes, and the purity of DNA. Therefore, standards are employed in order to account for the problem to know at which Cp (crossing point) or Ct (threshold cycle) value a given (known) amount of standard DNA can be detected. A dilution series of said standard DNA gives a standard curve, and allows for the normalization of differently performing/efficient RT-PCR systems. Since the quantification is performed on an equivalent system, differences in performance are normalized. However, the problem addressed concerns an (RT-)PCR that is performed on DNA aiming at the detection of biologically and/or chemically altered DNA. The complexity of this biologically and/or chemically altered DNA differs from normal/natural genomic DNA (starting by the simple fact that the complexity of the DNA molecules differ, since a plasmid consists of double stranded DNA of four bases (CTGA), whereas genomic DNA consists of double stranded five bases (CTGAC^(m)), and bisulfite converted DNA merely consists of only three single stranded bases (TGA)). Thus, the efficiency of amplification differs between the target DNA (i.e., human chromosomal genomic or bisulfite-converted DNA) and the standard DNA, if the standard is a plasmid or genomic DNA, but more importantly, the “amplification efficiency difference” between (plasmid) standard and the target DNA differs from amplification target to amplification target. (i.e., primer pair, probe etc.). This leads to a number of observations, when qPCR is performed on bisulfite treated and amplified DNA, such as, for example:

When different blood cells in a sample shall be measured, independently of method as used, the total cell number should be equivalent. However, in a given sample that is equally distributed for the performance of different qPCR-assays, despite the use of individual standards for each reaction the total number of copies as detected is different. This leads to the following problem (here shown with CD3 as an example) in case of (e.g.) blood samples that are measured using different RT-PCR systems:

TABLE 1 Calculation of overall DNA copy numbers and quantitative cell content following epigenetic qPCR using bisulfite-treated, amplified DNA of a blood sample. (CP) crossing point, (CN − BC) copy numbers bisulfite converted CD3⁺ marker DNA region, (CN − NBC) copy numbers non-bisulfite converted CD3⁺ marker DNA region, (CN − GAPDH) copy numbers bisulfite converted GAPDH marker DNA region. PCR for CD3⁺ bisulfite PCR for CD3⁺ non-bisulfite converted DNA converted DNA copy copy numbers numbers acc. to mean copy acc. to mean copy sample plasmid numbers sample plasmid numbers ID CP standard (CN − BC) ID CP standard (CN − NBC) WBL02 31.81 114.00 264.67 WBL02 27.01 1410.00 1413.33 WBL02 30.31 323.00 WBL02 26.99 1430.00 WBL02 30.17 357.00 WBL02 27.03 1400.00 WBL03 29.21 692.00 693.00 WBL03 27.46 1070.00 1053.33 WBL03 29.3  650.00 WBL03 27.53 1020.00 WBL03 29.12 737.00 WBL03 27.45 1070.00 PCR for GAPDH bisulfite converted DNA copy numbers acc. to mean copy Calculation overall DNA copy numbers sample plasmid numbers sample CN − BC + CN − NBC CN − GAPDH ID CP standard (CN − GAPDH) WBL02 1678 1420 WBL02 27.3  1520.00 1420.00 WBL03 1746.33 1383.33 WBL02 27.48 1350.00 WBL02 27.44 1390.00 WBL03 27.47 1360.00 1383.33 WBL03 27.43 1390.00 WBL03 27.42 1400.00 Calculation of % CD3⁺ cell content CN − BC × 100 CN − BC × 100 sample (CN − BC + CN − NBC) CN − GAPDH WBL02 15.8%   18% WBL03 36.6% 50.1%

As indicated in Table 1, calculated overall CD3⁺ DNA copy numbers differ between the two used standardization systems: bisulfite-converted vs. non-converted DNA and bisulfite-converted CD3⁺ marker region to bisulfite-converted GAPDH (overall cell) marker region. For the first blood sample (WBL02), number of CD3⁺ DNA copies calculated via number of GAPDH bisulfite converted DNA (1420 copies) is smaller than calculated via bisulfite converted added to non-bisulfite converted CD3⁺ DNA copy numbers (1678 copies). For the second sample (WBL03) the situation is similar. Differences become more obvious when using these calculated copy numbers for quantification of CD3⁺ cells within these two blood samples. For sample WBL02, quantification via bisulfite converted to non-converted DNA copy numbers results in 36.6% CD3⁺cells, whereas quantification via bisulfite converted CD3⁺ DNA copy numbers to bisulfite converted GAPDH DNA copy numbers results in 50.1% CD3⁺ cells. Both results and methods differ strongly.

As mentioned, even if normalization on a bisulfite-converted plasmid standard is performed, the different performances/efficiencies of the different assays do not lead to the same copy number.

This problem becomes particularly apparent, when purified cell types are measured with “their” specific epigenetic cell type markers, and compared to the total amount of cells in the sample (as measured by an cell-type unspecific marker (GAPDH)) as well as measured by non-bisulfite convertible DNA of a cell-type specific marker region (here FOXP3).

TABLE 2 Assessment of quantitative amount of regulatory T cell (Treg) within two samples of purified Tregs. DNA was isolated, bisulfite treated and relative amount of bisulfite converted and non- converted DNA assessed via qPCR. Copy numbers of bisulfite converted DNA in cell-specific FOXP3 regions were set in relation to copy numbers of bisulfite converted DNA in cell-unspecific GAPDH region as well as to bisulfite non-converted DNA in cell- type specific FOXP3 regions to obtain quantitative number of Tregs. (CP) crossing point), (CN-BC) copy numbers bisulfite converted cell-type specific FOXP3 DNA region, (CN-NBC) copy numbers non-bisulfite converted cell-type specific FOXP3 DNA region (CN-GAPDH) copy numbers bisulfite converted GAPDH DNA region. PCR for FOXP3 bisulfite converted DNA mean copy numbers sample acc. to plasmid ID CP standard (CN-BC) 88 27.52 2366.6 95 29.73 513.34 PCR for FOXP3 non-bisulfite converted DNA mean copy numbers sample acc. to plasmid ID CP standard (CN-NBC) 88 32.82 72.54 95 35.48 10.92 PCR for GAPDH bisulfite converted DNA mean copy numbers sample acc. to plasmid ID CP standard (CN-GAPDH) 88 26.6 2320.00 95 28.91 483.67 Calculation of % Treg cell content sample CN-BC × 100 CN-BC × 100 ID (CN-BC + CN-NBC) CN-GAPDH 88 97.03% 102% 95 97.92% 106%

As can be seen from table 2, again, results for both of the quantification methods differ strongly (97% vs. 102% and 97% vs. 106%).

Finally, when different cell fractions, e.g. blood leukocytes, are measured that, when added up, should make up all cells in the sample as present, the above problem makes it impossible to provide for a correct “complete blood count”. As an example for this, for two blood samples the leukocytes were quantified (Table 3, sample 04 and sample 08). Here, the term leukocytes summarize all the five types of white blood cells: granulocytes, monocytes, B-lympocytes, natural killer cells, and CD3⁺ T-lymphocytes. Accordingly, it was expected that the single cell counts sum up to 100%, representing a (complete) leukocytogram. However, when using epigenetic qPCR analyses, this is often not the case (see Table 3). The sum of individual quantities of leukocytes often differs from 100%.

TABLE 3 Assessment of the quantitative cell composition of two blood samples. DNA was isolated, bisulfite treated and relative amount of bisulfite converted DNA assessed via qPCR. Copy numbers of bisulfite converted DNA in cell-specific regions were set in relation to bisulfite converted copy numbers of the cell-unspecific DNA region for GAPDH to obtain quantitative number of leukocytes. (CN-BC) copy numbers bisulfite converted cell-type specific marker DNA region, (CN-GAPDH) copy numbers bisulfite converted GAPDH marker DNA region. Calculation of Leukocytogram (% of cells) sample04 sample08 CN-BC × 100 CN-BC × 100 cell type CN-GAPDH CN-GAPDH granulozytes 79.74% 81.29% monozytes 7.94% 11.05% B cells 1.63% 1.68% natural killer cells 2.74% 2.04% T cells 23.25% 22.09% Sum: 115.3 118.15

When summarizing the above mentioned problems of epigenetic cell quantification, a precise blood counting tool provides the following:

1. allows for the assessment of a precise, comprehensive blood and immune cell count, 2. overcomes differences in assay performance and/or efficiency between standards as used and the biological sample to be analyzed, 3. is independent of membrane integrity of cells to be counted (intact or non-intact cells), and 4. is independent of type of cell containing sample (fresh, frozen, embedded, stored, fluids, solid tissues).

The present invention provides such a tool, and respective methods. According to the present invention, assessing the epigenetic haemogram comprises measurement of the absolute amount of cells by normalization of qPCR results on a bisulfite-unconverted or -converted normalization standard. The normalization standards consist of a nucleic acid molecule comprising at least one marker-region being specific for each of the blood cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies, on said molecule and/or a natural blood cell sample of known composition.

In a first step of a preferred embodiment of the method, qPCR assay-specific correction factors are determined to achieve normalization and comparability of all qPCR assays as well as to correct for differences in assay efficiencies. In a second step, DNA of biological sample is isolated, purified and bisulfite treated. This is followed by qPCR specific for bisulfite-converted cell-type specific and/or cell-type unspecific genomic marker regions. The qPCR amplification results are then normalized with said normalization standard, which represents the relative amount of copies of marker DNA, and therefore the relative amount of specific cells. The normalization standard contains bisulfite-converted genomic marker regions or contains native, bisulfite-unconverted, marker regions. Before starting the qPCR, in the latter case the nucleic acid will be bisulfite treated in parallel to the biological sample as analyzed is treated. In a next step, following qPCR, the normalized relative amount of copies of marker DNA is corrected by an assay specific correction factor as described herein in order to correct for differences in assay efficiencies indicating the absolute amount of cells.

The present method allows for a quantification of non-intact but also intact blood cells in biological samples, such as, for example, dried, frozen, embedded, stored as well as fresh body fluids, dried blood spots, blood clots and tissue samples. The sample does not contain purified or enriched cells. Furthermore, the method of the present invention provides for a blood count, wherein the identity and quantity of cells is based on a clear yes/no information on the genomic level that is independent from protein expression levels.

The present invention thus provides a blood and/or immune cell count to be used as an analytical and diagnostic tool for medical use and as a basis for decisions in therapy.

Preferred is a method according to the present invention, furthermore comprising the step of obtaining a comprehensive blood picture, based on said detecting and quantifying. The blood cell count thus identifies the comprehensive picture of the cellular composition based on a number of epigenetic parameters. The combination of these epigenetic parameters is used to identify the cell composition of a blood or tissue sample, i.e. an epigenetic haemogram, and said epigenetic haemogram is provided based on the analysis of the bisulfite convertibility of cell-specific genomic regions.

Preferably, said epigenetic haemogram resembles a leukocytogram and/or a T-lymphocytogram and/or a granulocytogram and/or a monocytogram and/or a B-lymphocytogram and/or a NK cytogram.

Preferably, the method according to the present invention furthermore comprises the use of a bisulfite-unconverted or -converted normalization standard for the normalization, e.g. of the qPCR results. The term “bisulfite-unconverted” normalization standard encompasses natural DNA molecules containing the original/primary biologic modifications, such as formylation, carboxylation, methylation, or hydroxymethylation and that is not bisulfite-treated, and therefore bisulfite-unconverted. The term “bisulfite-converted” normalization standard encompasses DNA molecules containing (genomic) marker sequences corresponding to already bisulfite-converted cell-type specific and unspecific marker regions.

The bisulfite-unconverted or bisulfite-converted nucleic acid molecule is preferably selected from a plasmid, a yeast artificial chromosome (YAC), human artificial chromosome (HAC), P1-derived artificial chromosome (PAC), a bacterial artificial chromosome (BAC), and a PCR-product. Bisulfite-converted normalization standard is a plasmid, yeast artificial chromosomes (YAC), human artificial chromosome (HAC), P1-derived artificial chromosome (PAC), bacterial artificial chromosome (BAC) or a PCR-product.

The natural blood cell sample preferably is a blood sample of known cellular composition, and/or of known composition of blood cell types, and is preferably produced in advance, i.e. the amount and number blood cell types as combined is pre-determined.

In a preferred embodiment of the method according to the invention, the normalization standard, i.e. the plasmid, YAC, HAC, PAC, BAC, and PCR-product, contains cell-specific and unspecific genomic marker regions (to be analyzed in accordance with the epigenetic haemogram) in the same known number of copies on said molecule. In one embodiment, each of these standards is a single molecule containing the same number of all cell-type specific and unspecific genomic marker regions of interest in the epigenetic haemogram to be established. The natural blood cell sample (preferably mammalian, such as human) used as the bisulfite-unconverted normalization standard contains cells in a known composition and quantity, whereby cells can be pre-purified and pre-mixed to obtain a sample of known composition, that is also pre-determined.

During analytical processing, the bisulfite-unconverted normalization standard is bisulfite-treated in parallel and in the same fashion than the bisulfite treatment of the biological sample to be analyzed.

Then, qPCR on the unknown biological sample as well as on the (now) bisulfite-treated bisulfite-unconverted normalization standard is performed using specific primers that help to detect cell-type specific or unspecific bisulfite-converted genomic regions. In contrast, the bisulfite-converted normalization standard will (obviously) not be bisulfite-treated, as it already contains specific marker sequences that correspond to bisulfite-converted marker sequences recognized by qPCR primers that are specific for bisulfite-converted genomic regions.

In a preferred embodiment, the normalization standard comprises a predetermined amount of blood cells of the types to be detected and analyzed according to the haemogram. Preferably, a normalization standard is used consisting of a defined copy number and same stoichiometric amount of specific cells and/or of cell-type specific and/or cell-type unspecific marker regions. Preferred is a single plasmid containing the same copy number and/or stoichiometric amount of cell-type specific and/or cell-type unspecific marker regions for all cell types of interest for the haemogram.

A preferred embodiment of the method according to the invention furthermore comprises the step of correcting said epigenetic haemogram as produced with an assay specific correction factor. Said assay-specific correction factor (for the cells as detected and analyzed) is determined by comparing the known quantitative amount of cells in said mammalian natural cell sample as provided with the relative amount of copy numbers of bisulfite-converted cell-type specific marker DNA of said mammalian natural cell sample assessed by the qPCR using the normalization standard. Using this approach, the present method allows for an accurate quantification of cells, as any assay-specific variations that may have occurred are taken into account. Depending from the kind of normalization standard as used, the assay specific correction factors can differ. The more the normalization standard and its analytical processing are adapted to the biological sample and its processing, the more the assay specific correction factors will approach 1, or even can be neglected. In a preferred embodiment, a bisulfite-unconverted normalization standard is used as it resembles the complexity and impureness of natural cell samples, and therefore the qPCR efficiency between a biological sample and standard should be aligned. Most preferred is the use of a mammalian natural cell sample of known cell composition and quantity as described herein.

The method according to the present invention then comprises the step of determining the relative amount (of copies) of cell-type specific and unspecific DNA within the biological sample of unknown composition. This is achieved by qPCR on isolated, purified and bisulfite-converted DNA of said biological sample under the use of primers specific for bisulfite-converted cell-type specific and unspecific DNA marker sequences. qPCR amplification results for all target cell types are the normalized on said bisulfite-unconverted or converted standard indicating the relative amount of target cells. According to standards and assays used, specific assay correction factors are applied on relative amount of target cells to receive the absolute amount and percentage of the content of cells according to said haemogram as established. Thereby, the absolute, comprehensive cellular composition in said biological sample is determined. Depending from the normalization standard used, the assay correction factor differs from 1, or is approximately 1, and then can be neglected. Other methods for determining the relative amount (of copies) of cell-type specific and unspecific DNA comprise a method selected from specific enzymatic digests or dye exclusion technologies, bisulfate sequencing, next generation sequencing, nanopore sequencing, single molecule real-time sequencing, analyses of epigenetic modifications in promoter regions, using primers specific for bisulfite-converted DNA, using blocking oligonucleotides specific for bisulfite-converted DNA, using fluorescence-labeled, quenched oligonucleotide probes, using primers for single nucleotide primer extension specific for bisulfate-converted DNA, digital or quantitative PCR analysis, and specific selective (nucleic acid and/or chromatin) precipitation.

Preferred is a method according to the present invention, wherein the determination of the relative amount of target cells is based on comparing the amounts of copies of said bisulfite-converted cell-specific regions as determined with the amounts of copies of the bisulfate-converted regions that are unspecific for a cell-type as determined, thereby identifying the relative amount of a specific cell type in relation to all cells present in the sample.

In one embodiment according to the present invention, the relative amount of target cells is determined based on comparing the amounts of copies of said bisulfate-converted cell-specific regions as determined with the amounts of copies of bisulfite-unconverted cell-specific regions as determined, thereby identifying the relative amount of target cells in relation all other cells present in the sample.

In a preferred embodiment of the method according to the invention, further a knowledge base comprising information about cell-specific assay-correction factors estimated/calculated during previous assessments of epigenetic assays is generated. These values may be advantageously used in order to select particularly suitable normalization standards.

In a particularly preferred embodiment of the method according to the present invention, cell-type marker regions are detected that discriminate a specific cell type and/or at least one specific subpopulation of cells from other cells of a leukocytogram, a T-lymphocytogram, a granulocytogram, a monocytogram, a B-lymphocytogram and/or a NK-cytogram. Preferably, a) the leukocytogram consists of T-lymphocytes, natural killer cells, B-lymphocytes, monocytes and/or granulocytes, b) the T-lymphocytogram consists of CD3⁺CD4⁺, CD3⁺CD8⁺, CD8⁻CD4⁻, and/or CD8⁺CD4⁺ c) the granulocytogram consists of basophilic, eosinophilic, neutrophilicgranulocytes, and/or granulocytic myeloid-derived suppressor cells, d) the monocytogram consists of CD14⁺ monocytes, CD 14 ⁻ monocytes, macrophages, monocytic myeloid-derived suppressor cells, plasmacytoid dendritic cells, myeloid dendritic cells, and/or overall dendritic cells, c) the B-lymphocytogram consists of naïve B cells, pre-B cells, memory B cells, transitional B cells and/or immature B cells, and f) the NK cytogram consists of CD56^(dim) and/or CD56^(bright) NK cells.

Preferably, within the haemogram as determined sub-haemograms (or subpopulations) can be determined. Preferred is a T-helper-cytogram comprising, e.g., Th1, Th2, Th9, Th17, Th19, Th 21, Th22, Tfh, CD4⁺ natural killer cells (NKT), naïve CD4⁺, memory CD4⁺, effector CD4⁺ cells, and/or CD4⁺ regulatory T cells, or a T-cytotoxogram comprising, e.g., naïve CD8⁺, effector CD8⁺, memory CD8⁺, CD8⁺ natural killer cells (NKT), and/or CD8⁺ regulatory T cells. Furthermore, sub-populations of monocytes can be determined, comprising classical monocytcs (CD 14 ⁻), intermediate monocytes (CD 14 ⁺) and/or non-classical monocytes (CD 14 ⁺⁺) or a dendritogram comprising myeloid dendritic cells, and plasmacytoid dendritic cells. Future scientific studies may discover and identify yet unknown blood cells and leukocyte subgroups and may will assign new functions to certain blood cells and/or will assign known blood cells to different leukocyte subpopulations.

To determine the relative amount of bisulfite-convertible and/or non-bisulfite convertible DNA or nucleic acid comprises a method selected from specific enzymatic digests or dye exclusion technologies, bisulfite sequencing, next generation sequencing, nanopore sequencing, single molecule real-time sequencing, analyses of epigenetic modifications in promoter regions, using primers specific for bisulfite-converted DNA, using blocking oligonucleotides specific for bisulfite-converted DNA, using fluorescence-labeled, quenched oligonucleotide probes, using primers for single nucleotide primer extension specific for bisulfite-converted DNA, digital or quantitative PCR analysis, and specific selective (nucleic acid and/or chromatin) precipitation.

Further preferred is a method according to the present invention, wherein said normalization standard is bisulfite-unconverted and contains at least one bisulfite-convertible CpG position.

Further preferred is a method according to the present invention, wherein said quantifying of cell types in said biological sample is based on the normalization of the relative amount of cell-type specific and unspecific chromatin using the bisulfite-unconverted normalization standard or using the bisulfite-converted normalization standard.

Even further preferred is a method according to the present invention, wherein said normalization using the bisulfite-unconverted normalization standard is indicative for the absolute amount and/or percentage of content of cells within said biological sample

Even further preferred is a method according to the present invention, wherein said biological sample is a sample of unknown cellular composition.

The biological sample as analyzed in the context of the present invention is any sample that contains cells to be analyzed, i.e. cells of the blood and/or immune system, such as cells of a leukocytogram, selected from T-lymphocytes, natural killer cells, B lymphocytes, monocytes, and/or granulocytes, and combinations thereof; a T-lymphocytogram, selected from CD3⁺CD4⁺, CD4⁺ memory, CD4⁺ effector cells, CD4⁺ naïve, CD3⁺CD8⁺, CD8⁺ memory, CD8⁺ effector cells, CD8⁺ naïve, CD3⁺CD8⁻CD4⁻, CD3⁺CD8⁺CD4⁺, NKT cells, iTreg, Treg, Tfh, Th1, Th2, TH9, Th17, Th19, Th21, Th22, memory and/or effector T helper cells, and combinations thereof, a granulocytogram, selected from basophilic, eosinophilic, neutrophilic, overall neutrophil granulocytes, and/or granulocytic myeloid-derived suppressor cells, and combinations thereof, a monocytogram, selected from CD14⁺ monocytes, CD14− monocyes, macrophages, plasmacytoid dendritic cells, monocytic myeloid-derived suppressor cells, intermediate monocyets, classical monocytes, non-classical monocytes, and/or overall dendritic cells, and combinations thereof, a B-lymphocytogram, selected from naïve B cells, pre B cells, memory B cells, transitional B cells and/or immature B cells, and combinations thereof, and a NK cytogram, selected from CD56^(dim) and/or CD56^(bright) NK cells.

The term “cell-specific region(s)” herein shall mean genetic regions in the genome of cells and/or nucleic acids that are selected to discriminate on an epigenetic level one cell type and/or subpopulations of cells from all other cell types and/or subpopulations of cells. These regions include the genes of certain markers (such as, for example, certain protein markers), such as 5′ untranslated regions, promoter regions, introns, exons, intron/exon borders, 3′ regions, CpG islands, and in particular include specific regions as amplified after bisulfite treatment (amplicons) that are “informative” about the one cell type and/or subpopulations of cells. Examples for these cell-specific regions are known from the literature, such as, for example, the gene CD3 γ, δ and ε (WO 2010/069499); the granulysine gene (WO 2010/125106); the CCR6 gene (WO 2011/135088); the FOXP3 gene (WO 2004/050706 and Wieczorek et al. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 2009 Jan. 15; 69(2):599-608.)

Cell-specific marker region usually are DNA regions that contain single CpGs or CpG islands that are bisulfite-convertible only in a specific cell type and therefore indicative for the specific cell type. Additionally, these cell-specific marker regions discriminate one cell type from all other blood cells as well as other tissue cells.

According to the present invention, cells of the epigenetic haemogram are identified and quantified by analyzing the bisulfite convertibility of at least on CpG position in said cell-specific genomic regions.

Thus, preferred is a method according to the present invention, wherein a bisulfite conversion of at least one CpG position within a region as listed in the following table 4 is indicative for the respective blood cell type as listed in said table. These are e.g. the following genomic marker regions for the given cell types:

TABLE 4 cell-specific genomic regions SEQ ID Dis- cov- ery frag cyto- ment/ Gran- toxic SEQ Marker- ENSEMBL ulo- Mono- CD4+ T- B- NK- NK ID Pos ID TargetID SYMBOL Accession (ENSG #) cytes cytes cells cells cells cells T's ROI  1 NK_nm1 cg08766149 GZMB NM_004131 00100453 0.91 0.90 0.87 0.89 0.57 0.13  1/2  2 NK_nm2 cg22917487 CX3CR1 NM_001337 00168329 0.92 0.92 0.94 0.92 0.57 0.13  3/4  3 NK_nm3 cg12445208 ZNF583 NM_152478 00198440 0.77 0.83 0.76 0.64 0.73 0.18 0.54  5/6  4 NK_nm4 cg02196805 CSF2 NM_000758 00164400 0.78 0.78 0.50 0.60 0.77 0.22 0.52  7/8  5 NK_nm5 cg23617121 OSBPL5 NT_009237 00021762 0.95 0.95 0.92 0.89 0.85 0.22 0.81  9/10  6 NK_nm6 cg20697204 FLJ40172 NM_173649 00239605 0.78 0.89 0.91 0.83 0.73 0.23  11/12  7 NK_nm7 cg11801011 SHANK1 NM_016148 00161681 0.68 0.62 0.64 0.72 0.56 0.26  13/14  8 NK_nm8 cg07873128 OSBPL5 NT_009237 00021762 0.93 0.94 0.93 0.93 0.60 0.27  15/16  9 NK_nm9 cg03368758 LDB2 NM_001290 00169744 0.74 0.78 0.75 0.71 0.67 0.27 0.68  17/18  10 NK_nm10 cg00515905 EPS8L3 NM_024526 00198758 0.92 0.93 0.92 0.94 0.84 0.29  19/20  11 NK_nm11 cg22228134 GZMH NM_033423 00100450 0.83 0.90 0.90 0.89 0.53 0.30  21/22  12 NK_nm12 cg26379475 SH2D1B NM_053282 00198574 0.79 0.79 0.64 0.64 0.59 0.32 0.61  23/24  13 NK_nm13 cg04384208 FCGR3A NM_000569 00203747 0.84 0.87 0.82 0.83 0.71 0.32  25/26  14 NK_nm14 cg00453258 FAM26C NM_001001412 00185933 0.71 0.71 0.85 0.82 0.92 0.33  27/28  15 NK_nm15 cg06827976 FGR NM_005248 00000938 0.78 0.83 0.88 0.80 0.78 0.35 0.60  29/30  16 NK_nm16 cg12491710 LIM2 NM_030657 00105370 0.95 0.94 0.93 0.93 0.86 0.36  31/32  17 NK_nm17 cg18250832 NMUR1 NM_006056 00171596 0.76 0.72 0.78 0.74 0.77 0.38  33/34  18 NK_nm18 cg15544721 PPP1R9A XM_371933 00158528 0.64 0.76 0.85 0.88 0.53 0.38  35/36  19 NK_nm19 cg25943702 BRD1 NM_014577 00100425 0.80 0.84 0.80 0.78 0.73 0.38 0.71  37/38  20 NK_nm20 cg04230060 SUSD1 NM_022486 00106868 0.69 0.69 0.91 0.87 0.71 0.39 0.84  39/40  21 NK_nm21 cg06229674 ARP10 NM_181773 00100298 0.94 0.95 0.93 0.92 0.50 0.40  41/42  22 NK_nm22 cg14701962 C1orf111 NM_182581 00171722 0.81 0.85 0.79 0.77 0.74 0.41 0.69  43/44  23 NK_nm23 cg16522484 C14orf49 NM_152592 00176438 0.72 0.80 0.74 0.74 0.53 0.42  45/46  24 NK_nm24 cg26738080 TNNC1 NM_003280 00114854 0.84 0.76 0.87 0.86 0.66 0.42  47/48  25 NK_nm25 cg13525683 TIAF1 NM_004740 00221995 0.81 0.83 0.78 0.77 0.75 0.42 0.75  49/50  26 NK_nm26 cg23352030 PRIC285 NM_033405 00130589 0.85 0.82 0.95 0.94 0.90 0.43  51/52  27 NK_nm27 cg23282949 RENBP NM_002910 00102032 0.72 0.76 0.91 0.85 0.86 044 0.81  53/54  28 NK_nm28 cg00491404 EPS8L3 NM_024526 00198758 0.88 0.83 0.88 0.87 0.79 0.45  55/56  29 NK_nm29 cg25903122 MGC2747 NM_024104 00214046 0.87 0.92 0.92 0.89 0.68 0.48  57/58  30 NK_nm30 cg22202141 FCGR3A NM_000569 00203747 0.90 0.87 0.88 0.89 0.58 0.48  59/60  31 NK_nm3l cg11094938 ATP2A1 NM_173201 00196296 0.91 0.85 0.90 0.90 0.92 0.49  61/62  32 NK_nm32 cg23580000 ADCY7 NM_001114 00121281 0.80 0.81 0.96 0.94 0.92 0.49  63/64  33 NK_m1 cg12167564 LYST NM_000081 00143669 0.30 0.13 0.47 0.50 0.36 0.68 0.37  65/66  34 NK_m2 cg18881723 SLAMF1 NM_003037 00117090 0.03 0.03 0.03 0.05 0.08 0.66  67/68  35 NK_m3 cg18096388 PDCD1 NM_005018 00188389 0.41 0.50 0.11 0.20 0.36 0.65 0.25  69/70  36 NK_m5 cg27016307 HRC NM_002152 00130528 0.46 0.44 0.21 0.33 0.30 0.56 0.11  71/72  37 NK_m6 cg18818531 FOSL1 NM_005438 00175592 0.40 0.42 0.17 0.17 0.37 0.56 0.25  73/74  38 NK_m7 cg27067618 CYP4F3 NM_000896 00186529 0.15 0.29 0.38 0.41 0.40 0.55 0.23  75/76  39 NK_m8 cg04790129 ITGB2 NM_000211 00160255 0.13 0.24 0.35 0.40 0.13 0.54 0.39  77/78  40 NK_m9 cg25944100 MS4A3 NM_006138 00149516 0.10 0.20 0.46 0.41 0.40 0.54 0.38  79/80  41 NK_m10 cg09076123 NCF2 NM_000433 00116701 0.03 0.07 0.28 0.31 0.24 0.53 0.13  81/82  42 NK_m11 cg05275752 GALM NM_138801 00143891 0.19 0.18 0.29 0.44 0.30 0.52 0.33  83/84  43 NK_m12 cg19030554 NME3 NM_002513 00103024 0.15 0.36 0.29 0.34 0.49 0.51  85/86  44 NKT_n1 cg02833725 ISG20L2 NM_030980 00143319 0.81 0.86 0.52 0.55 0.63 0.88 0.15  87/88  45 NKT_n2 cg06736444 SRRM2 NM_016333 00167978 0.84 0.87 0.59 0.59 0.53 0.86 0.25  89/90  46 NKT_n3 cg14862827 SUSD1 NM_022486 00106868 0.62 0.62 0.59 0.71 0.55 0.65 0.17  91/92  47 NKT_n4 cg06154597 MGC4618 NM_032326 00127419 0.82 0.84 0.61 0.58 0.83 0.62 0.27  93/94  48 NKT_n5 cg17267907 DEFA1 NM_004084 00239839 0.80 0.83 0.71 0.54 0.77 0.56 0.32  95/96  49 NKT_n6 cg15210427 CST9L NM_080610 00101435 0.82 0.88 0.56 0.63 0.62 0.79 0.34  97/98   50 NKT_n7 cg08603768 WNT8A NM_031933 00061492 0.81 0.81 0.54 0.51 0.59 0.66 0.28  99/100  51 NKT_n8 cg14366490 TXNL6 NM_138454 00171773 0.81 0.81 0.51 0.56 0.58 0.74 0.30 101/102  52 NKT_n9 cg25827666 NTRK1 NM_001007792 00198400 0.86 0.86 0.63 0.64 0.82 0.57 0.36 103/104  53 NKT_n10 cg10624445 CNGB1 NM_001297 00070729 0.83 0.86 0.58 0.58 0.64 0.82 0.35 105/106  54 NKT_n11 cg01605984 SURF5 NM_181491 00148297 0.77 0.86 0.51 0.55 0.62 0.81 0.32 107/108  55 NKT_n12 cg20661303 LEFTY2 NM_003240 00143768 0.74 0.75 0.59 0.65 0.77 0.86 0.39 109/110  56 NKT_n13 cg12240237 WBSCR23 NM_025042 00006704 0.84 0.86 0.51 0.53 0.60 0.77 0.36 111/112  57 NKT_n14 cg14375111 TMEM43 NM_024334 00170876 0.92 0.95 0.62 0.61 0.65 0.89 0.45 113/114  58 NKT_n15 cg19464252 FBS1 NM_022452 00156860 0.86 0.90 0.62 0.54 0.55 0.83 0.40 115/116  59 NKT_n16 cg14076161 PRB4 NM_002723 00230657 0.82 0.78 0.52 0.53 0.64 0.76 0.36 117/118  60 NKT_n17 cg10848367 SCGB1D2 NM_006551 00124935 0.78 0.78 0.55 0.60 0.56 0.68 0.34 119/120  61 NKT_n18 cg00626119 NTRK1 NM_001007792 00198400 0.79 0.82 0.59 0.61 0.80 0.57 0.38 121/122  62 NKT_n19 cg13881341 FUT1 NM_000148 00174951 0.88 0.86 0.65 0.67 0.69 0.80 0.45 123/124  63 NKT_n20 cg10779183 ELA3A NM_005747 00142789 0.84 0.85 0.58 0.64 0.70 0.72 0.42 125/126  64 NKT_m13 cg00754253 HRASLS5 NM_054108 00168004 0.09 0.37 0.33 0.40 0.44 0.50 0.70 127/128  65 NKT_m12 cg13492227 FGF11 NM_004112 00161958 0.17 0.20 0.50 0.45 0.31 0.38 0.69 129/130  66 NKT_m1 cg07233761 ESM1 NM_007036 00164283 0.09 0.08 0.37 0.38 0.05 0.16 0.68 131/132  67 NKT_m2 cg03973663 LYN NM_002350 00254087 0.12 0.11 0.39 0.42 0.24 0.14 0.66 133/134  68 NKT_m6 cg09082287 DNAJC6 NM_014787 00116675 0.15 0.15 0.41 0.35 0.30 0.24 0.66 135/136  69 NKT_m7 cg14289511 FLJ45256 NM_207448 00224310 0.09 0.10 0.45 0.40 0.23 0.12 0.62 137/138  70 NKT_m8 cg03682712 LOXL1 NM_005576 00129038 0.04 0.12 0.47 0.46 0.23 0.10 0.62 139/140  71 NKT_m3 cg16907566 COL14A1 NM_021110 00187955 0.14 0.14 0.28 0.35 0.19 0.13 0.62 141/142  72 NKT_m5 cg22854223 CD82 NM_002231 00085117 0.04 0.04 0.42 0.43 0.13 0.19 0.61 143/144  73 NKT_m15 cg01305421 IGF1 NM_000618 00017427 0.07 0.06 0.42 0.47 0.24 0.36 0.61 145/146  74 NKT_m17 cg05989054 GAMT NM_000156 00130005 0.08 0.08 0.44 0.37 0.11 0.17 0.55 147/148  75 NKT_m4 cg26482939 GNA15 NM_002068 00060558 0.06 0.04 0.24 0.28 0.09 0.10 0.55 149/150  76 NKT_m16 cg20876010 CACHD1 NM_020925 00158966 0.12 0.12 0.31 0.28 0.20 0.18 0.54 151/152  77 NKT_m19 cg15526708 TGFBR1 NM_004612 00106799 0.15 0.13 0.31 0.36 0.13 0.15 0.54 153/154  78 NKT_m14 cg22799850 FBXL13 NM_145032 00161040 0.07 0.07 0.31 0.48 0.07 0.18 0.54 155/156  79 NKT_m18 cg13105904 KIAA0323 NM_015299 00100441 0.13 0.20 0.13 0.28 0.16 0.30 0.53 157/158  80 NKT_m20 cg22268231 SPIB NM_003121 00269404 0.13 0.08 0.36 0.45 0.06 0.14 0.53 159/160  81 NKT_m10 cg10784030 INPP5B NM_005540 00204084 0.08 0.08 0.23 0.17 0.11 0.13 0.49 161/162  82 NKT_m11 cg19766460 C21orf128 NM_152507 00184385 0.04 0.04 0.06 0.24 0.04 0.06 0.44 163/164  83 B_nm1 cg00226923 FGD2 NM_173558 00146192 0.93 0.96 0.95 0.96 0.10 0.95 165/166  84 B_nm2 cg03860768 BLK NM_001715 00136573 0.83 0.88 0.87 0.86 0.1I 0.82 167/168  85 B_nm3 cg16280667 BLR1 NM_001716 00160683 0.88 0.87 0.87 0.90 0.14 0.89 169/170  86 B_nm4 cg14127336 TCL1A NM_021966 00100721 0.92 0.92 0.92 0.92 0.14 0.93 171/172  87 B_nm5 cg22679120 SNX8 NM_013321 00106266 0.64 0.65 0.59 0.63 0.15 0.72 0.64 173/174  88 B_nm6 cg16698623 MGMT NT_008818 00170430 0.95 0.94 0.96 0.97 0.15 0.93 175/176  89 B_nm7 cg10115873 DNAJB7 NM_145174 00172404 0.68 0.80 0.80 0.75 0.16 0.79 177/178  90 B_nm8 cg27394566 PLD4 NM_138790 00166428 0.72 0.56 0.88 0.89 0.16 0.85 179/180  91 B_nm9 cg14102807 CD19 NM_001770 00177455 0.88 0.90 0.92 0.93 0.16 0.89 181/182  92 B_nm10 cg17399166 CD1D NM_001766 00158473 0.89 0.81 0.88 0.88 0.17 0.87 183/184  93 B_nm11 cg22194129 CLEC4C NM_130441 00198178 0.85 0.88 0.90 0.92 0.17 0.85 185/186  94 B_nm12 cg15121304 — — 00197549 0.89 0.85 0.73 0.80 0.18 0.64 187/188  95 B_nm13 cg18979762 EGLN1 NM_022051 00135766 0.80 0.84 0.83 0.81 0.19 0.72 189/190  96 B_nm14 cg03221619 FCER2 NM_002002 00104921 0.80 0.73 0.75 0.71 0.19 0.76 0.59 191/192  97 B_nm15 cg07597976 CD19 NM_001770 00177455 0.72 0.63 0.63 0.68 0.20 0.60 0.58 193/194  98 B_nm16 cg00126698 BTK NM_000061 00010671 0.63 0.62 0.86 0.77 0.20 0.76 0.81 195/196  99 B_nm17 cg16098726 GP9 NM_000174 00169704 0.71 0.82 0.92 0.91 0.20 0.87 197/198 100 B_nm18 cg02630207 FLJ10379 NM_018079 00068784 0.73 0.74 0.71 0.68 0.21 0.65 0.67 199/200/ 101 B_nm19 cg07790638 LOC91431 NM_138698 — 0.85 0.87 0.83 0.82 0.21 0.79 201/202 102 B_nm20 cg06667406 AASS NM_005763 00008311 0.85 0.84 0.85 0.83 0.22 0.81 203/204 103 B_nm21 cg26574610 VPREB3 NM_013378 00128218 0.81 0.84 0.87 0.89 0.22 0.83 205/206 104 B_nm22 cg07426848 S100A3 NM_002960 00188015 0.88 0.89 0.93 0.92 0.22 0.87 207/208 105 B_nm23 cg23984130 — 0.80 0.80 0.69 0.60 0.24 0.59 0.68 209/210 106 B_nm24 cg00113020 LILRB4 NM_006847 00186818 0.78 0.77 0.77 0.69 0.24 0.56 0.73 211/212 107 B_nm25 cg25769980 TLR6 NM_006068 00174130 0.90 0.90 0.87 0.87 0.25 0.81 213/214 108 B_nm26 cg16873863 SLC22A18 NM_183233 00110628 0.59 0.61 0.75 0.76 0.25 0.74 0.71 215/216 109 B_nm27 cg22295573 AQP4 NM_001650 00171885 0.87 0.90 0.87 0.89 0.25 0.84 217/218 110 B_nm28 cg18075299 C14orf54 NM_173526 00172717 0.84 0.89 0.85 0.89 0.26 0.86 219/220 111 B_nm29 cg02399455 SRI NM_198901 00075142 0.88 0.87 0.90 0.86 0.26 0.78 221/222 112 B_nm30 cg10762615 FBXW10 NM_031456 00171931 0.88 0.89 0.88 0.85 0.26 0.83 223/224 113 B_nm31 cg18557145 CD72 NM_001782 00137101 0.80 0.87 0.89 0.91 0.26 0.83 0.84 225/226 114 B_nm32 cg00374717 ARSG NM_014960 00141337 0.90 0.91 0.85 0.85 0.26 0.85 227/228 115 B_nm33 cg19437319 KIAA0196 NM_014846 00164961 0.90 0.89 0.86 0.84 0.26 0.87 229/230 116 B_nm34 cg14959707 ZC3H7A NM_014153 00122299 0.89 0.89 0.89 0.92 0.27 0.89 231/232 117 B_nm35 cg18152830 TNFRSF13B NM_012452 00240505 0.92 0.91 0.86 0.91 0.27 0.91 0.86 233/234 118 B_nm36 cg16593081 DYX1C1 NM_001033559 00256061 0.91 0.92 0.89 0.88 0.28 0.87 235/236 119 B_nm37 cg26394380 SFTPB NM_000542 00168878 0.66 0.80 0.72 0.75 0.29 0.86 0.70 237/238 120 B_nm38 cg01909245 LSP1 NM_002339 00130592 0.87 0.84 0:64 0.63 0.30 0.71 0.62 239/240 121 B_nm39 cg03270204 DDR1 NM_001954 00204580 0.94 0.92 0.84 0.92 0.31 0.94 241/242 122 B_nm40 cg11042320 PDGFRB NM_002609 00113721 0.67 0.74 0.73 0.79 0.32 0.63 0.73 243/244 123 B_nm41 cg08251036 MGAT5 NM_002410 00152127 0.83 0.87 0.83 0.79 0.32 0.68 0.83 245/246 124 B_nm42 cg05921699 CD79A NM_001783 00105369 0.84 0.81 0.80 0.67 0.32 0.70 0.78 247/248 125 B_nm43 cg25211252 KCNMB3 NM_014407 00171121 0.86 0.83 0.83 0.83 0.34 0.83 0.80 249/250 126 B_nm44 cg21960110 HBZ NM_005332 00130656 0.85 0.88 0.80 0.69 0.36 0.81 0.57 251/252 127 B_m1 cg27398547 C14orf39 NM_174978 00179008 0.27 0.19 0.22 0.21 0.73 0.26 253/254 128 B_m2 cg22226839 ATP2B4 NM_001684 00058668 0.16 0.18 0.25 0.23 0.72 0.34 255/256 129 B_m3 cg11997899 DLX5 NM_005221 00105880 0.30 0.23 0.29 0.21 0.72 0.28 257/258 130 B_m4 cg19350340 ASPM NM_018136 00066279 0.14 0.13 0.16 0.20 0.72 0.22 259/260 131 B_m5 cg00049986 C14orf10 NM_017917 00092020 0.17 0.11 0.21 0.17 0.70 0.20 261/262 132 B_m6 cg08360728 GPATC3 NM_022078 00198746 0.28 0.31 0.33 0.24 0.69 0.31 263/264 133 B_m7 cg01222684 TTC1 NM_003314 00113312 0.06 0.05 0.10 0.05 0.66 0.14 265/266 134 B_m8 cg00571634 WDR5B NM_019069 00196981 0.18 0.18 0.16 0.16 0.65 0.20 267/268 135 B_m9 cg18908499 C1orf150 NM_145278 00169224 0.13 0.13 0.20 0.16 0.65 0.23 269/270 136 B_m10 cg00678539 MNS1 NM_018365 00138587 0.12 0.13 0.19 0.18 0.60 0.15 271/272 137 B_m11 cg19756611 DACH1 NM_004392 00165659 0.17 0.07 0.15 0.14 0.59 0.26 273/274 138 B_m12 cg23668631 CAMKK1 NM_032294 00004660 0.10 0.22 0.36 0.44 0.58 0.44 0.35 275/276 139 B_m13 cg18967846 CLDN12 NM_012129 00157224 0.14 0.14 0.16 0.10 0.58 0.24 277/278 140 B_m14 cg25482967 MRPS10 NM_018141 00048544 0.12 0.09 0.14 0.11 0.56 0.17 279/280 141 B_m15 cg06751597 SNAP23 NM_003825 00092531 0.07 0.07 0.11 0.09 0.56 0.07 281/282 142 B_m16 cg22285621 SSH3 NM_018276 00172830 0.01 0.08 0.05 0.11 0.55 0.07 283/284 143 B_m17 cg17378989 ERCC1 NM_202001 00012061 0.11 0.12 0.12 0.12 0.55 0.17 285/286 144 B_m18 cg03825921 RAB4A NM_004578 00168118 0.11 0.11 0.14 0.13 0.55 0.18 287/288 145 B_m19 cg11250058 RAPH1 NM_203365 00173166 0.06 0.08 0.07 0.24 0.55 0.09 289/290 146 B_m20 cg03643709 VPS18 NM_020857 00104142 0.18 0.13 0.19 0.10 0.54 0.22 291/292 147 B_m21 cg24641737 DENND2D NM_024901 00162777 0.03 0.03 0.04 0.03 0.54 0.05 293/294 148 B_m22 cg07732037 MPHOSPH9 NM_022782 00051825 0.27 0.47 0.06 0.10 0.53 0.25 0.09 295/296 149 B_m23 cg05091653 SP100 NM_003113 00067066 0.08 0.06 0.04 0.05 0.52 0.06 297/298 150 B_m24 cg16007628 ZNF207 NM_001032293 00010244 0.13 0.15 0.17 0.15 0.52 0.18 0.22 299/300 151 B_m25 cg26954174 CARD15 NM_022162 00167207 0.07 0.07 0.25 0.38 0.51 0.14 0.26 301/302 152 B_m26 cg01988129 ADHFE1 NM_144650 00147576 0.16 0.18 0.20 0.22 0.50 0.20 0.19 303/304 153 CD8_nm1 cg18149207 RORC NM_005060 00143365 0.83 0.87 0.65 0.31 0.65 0.75 305/306 154 CD8_nm2 cg02519218 CHFR NT_024477 00072609 0.85 0.84 0.52 0.39 0.60 0.71 0.62 307/308 155 CD8_nm3 cg21755709 C21orf124 NM_032920 00136014 0.66 0.71 0.65 0.43 0.63 0.64 0.66 309/310 156 CD8_nm4 cg24019564 RUNX3 NT_004610 00020633 0.55 0.75 0.67 0.44 0.74 0.51 0.62 311/312 157 CD8_nm5 cg19700658 UCP3 NM_003356 00175564 0.83 0.84 0.69 0.44 0.78 0.54 0.54 313/314 158 CD8_nm6 cg14027234 CD248 NM_020404 00174807 0.83 0.83 0.82 0.45 0.71 0.82 315/316 159 CD8_nm7 cg03024246 JRKL NM_003772 00183340 0.69 0.78 0.77 0.45 0.53 0.63 0.67 317/318 160 CD8_nm8 cg21232015 CHFR NT_024477 00072609 0.87 0.88 0.61 0.46 0.63 0.81 0.73 319/320 161 CD8_nm9 cg12108912 MGC10993 NM_030577 00144120 0.82 0.85 0.50 0.47 0.57 0.73 0.77 321/322 162 CD8_nm10 cg17505463 GGT3 NM_002058 00197421 0.82 0.80 0.59 0.47 0.69 0.66 0.60 323/324 163 CD8_nm11 cg07232688 LRRC39 NM_144620 00122477 0.71 0.75 0.72 0.47 0.59 0.50 0.64 325/326 164 CD8_m1 cg26848126 CYSLTR1 NM_006639 00173198 0.12 0.04 0.18 0.72 0.26 0.10 327/328 165 CD8_m3 cg25511807 MMP7 NM_002423 00137673 0.09 0.09 0.43 0.62 0.27 0.44 329/330 166 CD8_m4 cg16604516 FBLN2 NM_001004019 00163520 0.19 0.15 0.40 0.61 0.16 0.15 331/332 167 CD8_m5 cg23771929 FREQ NM_014286 00107130 0.20 0.21 0.46 0.60 0.28 0.34 0.46 333/334 168 CD8_m6 cg20340242 IL1R2 NM_004633 00115590 0.03 0.04 0.44 0.60 0.18 0.42 335/336 169 CD8_m7 cg09106999 CDK2 NM_001798 00123374 0.07 0.08 0.48 0.60 0.29 0.29 337/338 170 CD8_m8 cg00516481 PDE9A NM_002606 00160191 0.19 0.18 0.49 0.57 0.18 0.32 0.46 339/340 171 CD8_m9 cg22054164 ECE1 NM_001397 00117298 0.17 0.09 0.28 0.57 0.17 0.42 341/342 172 CD8_m10 cg06415153 PITPNM2 NM_020845 00090975 0.19 0.12 0.39 0.56 0.22 0.40 343/344 173 CD8_m11 cg22778947 FSD1NL NM_031919 00106701 0.16 0.18 0.50 0.55 0.18 0.33 345/346 174 CD8_m12 cg03627896 LOC283932 NM_175901 — 0.34 0.41 0.31 0.53 0.21 0.31 0.12 347/348 175 CD8_m13 cg00833777 ITGAM NM_000632 00169896 0.08 0.09 0.42 0.52 0.25 0.16 349/350 176 CD8_m14 cg01356829 IL12RB2 NM_001559 00081985 0.08 0.07 0.38 0.52 0.15 0.12 0.16 351/352 177 CD8_m15 cg18661868 FES NM_002005 00182511 0.08 0.11 0.34 0.51 0.29 0.13 353/354 178 CD8_m16 cg08899626 LDB2 NM_001290 00169744 0.05 0.09 0.18 0.51 0.18 0.12 355/356 179 CD8_m17 cg14700707 NOTCH4 NM_004557 00204301 0.05 0.05 0.39 0.50 0.14 0.35 0.30 357/358 180 CD4_nm1 cg03602500 FLJ00060 NM_033206 00104970 0.86 0.85 0.26 0.52 0.66 0.87 359/360 181 CD4_nm2 cg16470760 CD4 NM_000616 00010610 0.74 0.70 0.31 0.61 0.68 0.66 0.67 361/362 182 CD4_nm3 cg02989940 ERAF NM_016633 00169877 0.90 0.87 0.39 0.64 0.55 0.79 0.72 363/364 183 CD4_nm4 cg22972055 UNC84A NM_025154 00164828 0.91 0.93 0.42 0.64 0.50 0.89 365/366 184 CD4_nm5 cf29335340 PTPN6 NM_002831 00111679 0.66 0.73 0.42 0.64 0.59 0.78 0.57 367/368 185 CD4_nm6 cg08214029 CCL18 NM_002988 00006074 0.74 0.78 0.42 0.76 0.58 0.80 0.72 369/370 186 CD4_nm7 cg02385474 PCNXL2 NM_024938 00135749 0.78 0.78 0.43 0.52 0.54 0.65 0.62 371/372 187 CD4_nm8 cg01782486 ZBTB7B NM_015872 00160685 0.75 0.82 0.44 0.88 0.52 0.81 0.83 373/374 188 CD4_nm9 cg25598083 ACOT2 NM_006821 00119673 0.85 0.86 0.44 0.55 0.65 0.72 0.54 375/376 189 CD4_nm10 cg07327347 AQP8 NM_001169 00103375 0.88 0.65 0.46 0.70 0.67 0.79 0.54 377/378 190 CD4_nm11 cg12703269 PSTPIP1 NM_003978 00140368 0.82 0.82 0.46 0.61 0.80 0.84 0.59 379/380 191 CD4_nm12 cg23909633 IL24 NM_181339 00162892 0.87 0.87 0.48 0.65 0.74 0.76 0.80 381/382 192 CD4_nm13 cg18669588 PTK9L NM_007284 00247596 0.80 0.83 0.50 0.64 0.75 0.77 0.62 383/384 193 CD4_m1 cg25655096 GPR92 NM_020400 00184574 0.44 0.19 0.69 0.49 0.19 0.13 385/386 194 CD4_m2 cg05697976 MLSTD1 NM_018099 00064763 0.09 0.14 0.62 0.50 0.42 0.36 0.48 387/388 195 CD4_m3 cg10521852 EDG4 NM_004720 00064547 0.07 0.08 0.61 0.41 0.22 0.22 0.35 389/390 196 CD4_m4 cg08159444 PNMA5 NM_052926 00198883 0.26 0.06 0.61 0.48 0.48 0.46 391/392 197 CD4_m5 cg00443307 KLRG1 NM_005810 00139187 0.37 0.22 0.60 0.38 0.34 0.35 0.29 393/394 198 CD4_m6 cg04541607 CRYBB1 NM_001887 00100122 0.06 0.10 0.59 0.46 0.14 0.47 395/396 199 CD4_m7 cg03085312 RARA NM_001024809 00131759 0.16 0.15 0.59 0.38 0.18 0.17 0.39 397/398 200 CD4_m8 cg20764656 GPX2 NM_002083 00176153 0.04 0.06 0.58 0.47 0.17 0.12 0.34 399/400 201 CD4_m9 cg07837085 SLAMF7 NM_021181 00026751 0.06 0.07 0.57 0.35 0.27 0.07 401/402 202 CD4_m10 cg18440048 ZNF70 NM_021916 00187792 0.12 0.17 0.56 0.21 0.13 0.20 0.34 403/404 203 CD4_m11 cg18752880 C1QTNF3 NM_181435 00082196 0.06 0.29 0.56 0.46 0.46 0.15 0.21 405/406 204 CD4_m12 cg24576425 GALNT5 NM_014568 00136542 0.11 0.08 0.56 0.46 0.26 0.24 0.46 407/408 205 CD4_m13 cg18055007 DDAH2 NM_013974 00226634 0.11 0.08 0.55 0.21 0.15 0.13 0.14 409/410 206 CD4_m14 cg14913610 KLRG1 NM_005810 00139187 0.06 0.07 0.55 0.43 0.18 0.16 0.17 411/412 207 CD4_m15 cg00563926 TGFBR3 NM_003243 00069702 0.11 0.10 0.55 0.15 0.18 0.17 0.38 413/414 208 CD4_m16 cg05252264 FCAR NM_002000 00186431 0.06 0.08 0.55 0.47 0.21 0.38 415/416 209 CD4_m17 cg16465939 KCNQ1 NT_009237 00053918 0.05 0.05 0.54 0.22 0.28 0.11 417/418 210 CD4_m18 cg19963522 PIP3-E NM_015553 00074706 0.09 0.11 0.54. 0.38 0.19 0.32 0.46 419/420 211 CD4_m19 cg05512099 PLEKHF1 NM_024310 00166289 0.15 0.19 0.54 0.42 0.18 0.11 0.21 421/422 212 CD4_m20 cg07376232 AMICA1 NM_153206 00160593 0.05 0.03 0.52 0.36 0.21 0.20 423/424 213 CD4_m21 cg18059933 TP53INP1 NM_033285 00164938 0.23 0.16 0.50 0.43 0.10 0.10 0.31 425/426 214 MOC_nm1 cg02780988 KRTHA6 NM_003771 00126337 0.71 0.08 0.69 0.64 0.54 0.64 0.62 427/428 215 MOC_nm2 cg18854666 SLC11A1 NM_000578 00018280 0.61 0.14 0.94 0.94 0.79 0.92 429/430 216 MOC_nm3 cg18589858 SLCO2B1 NM_007256 00137491 0.73 0.15 0.89 0.86 0.58 0.81 431/432 217 MOC_nm4 cg22456522 LILRB3 NM_006864 00204577 0.84 0.17 0.80 0.83 0.68 0.80 433/434 218 MOC_nm5 cg27443224 CCL21 NM_002989 00137077 0.67 0.17 0.63 0.60 0.52 0.52 0.64 435/436 219 MOC_nm6 cg22954818 APOBEC3A NM_145699 00128383 0.55 0.20 0.65 0.61 0.50 0.65 0.64 437/438 220 MOC_nm7 cg05445326 TM4SF19 NM_138461 00145107 0.91 0.21 0.93 0.93 0.58 0.64 439/440 221 MOC_nm8 cg10045881 CHI3L2 NM_001025197 00064886 0.61 0.21 0.66 0.73 0.62 0.69 0.77 441/442 222 MOC_nm9 cg11051139 LOC144501 NM_182507 00167767 0.58 0.21 0.76 0.77 0.74 0.70 0.71 443/444 223 MOC_nm11 cg01193293 SIGLEC7 NM_014385 00168995 0.65 0.29 0.66 0.66 0.60 0.50 445/446 224 MOC_nm12 cg04387658 CD86 NM_006889 00114013 0.55 0.33 0.76 0.72 0.58 0.57 0.80 447/448 225 MOC_nm13 cg22319147 CDH5 NM_001795 00179776 0.56 0.34 0.95 0.95 0.72 0.90 449/450 226 MOC_nm14 cg13253729 Rgr NM_153615 00159496 0.85 0.41 0.94 0.93 0.53 0.90 451/452 227 MOC_nm15 cg00412772 C19orf33 NM_033520 00167644 0.57 0.42 0.74 0.72 0.52 0.62 453/454 228 MOC_nm16 cg07986773 NUP50 NM_153645 00093000 0.85 0.42 0.90 0.89 0.77 0.83 455/456 229 MOC_nm17 cg06407137 CD300LB NM_174892 00178789 0.78 0.42 0.84 0.79 0.80 0.74 0.85 457/458 230 MOC_nm18 cg12564453 CETP NM_000078 00087237 0.61 0.44 0.95 0.94 0.65 0.66 459/460 231 MOC_nm19 cg02497428 IGSF6 NM_005849 00140749 0.92 0.48 0.95 0.95 0.77 0.94 461/462 232 MOC_nm20 cg16501235 C1orf54 NM_024579 00118292 0.83 0.48 0.86 0.82 0.75 0.83 0.81 463/464 233 MOC_meth1 cg05044994 FLJ42393 NM_207488 00213132 0.47 0.74 0.16 0.24 0.32 0.17 465/466 234 MOC_meth2 cg23213217 DEGS1 NM_144780 00143753 0.04 0.73 0.04 0.03 0.24 0.38 467/468 235 MOC_meth3 cg24921858 BCL2L14 NM_030766 00121380 0.48 0.64 0.44 0.42 0.22 0.46 469/470 236 MOC_mcth4 cg07747299 C21orf56 NM_032261 00160284 0.47 0.63 0.39 0.35 0.34 0.37 0.27 471/472 237 MOC_meth5 cg20839025 PRSS7 NM_002772 00154646 0.43 0.63 0.43 0.38 0.40 0.31 0.32 473/474 238 MOC_meth6 cg15551881 TRAF1 NM_005658 00056558 0.08 0.62 0.16 0.06 0.48 0.21 475/476 239 MOC_meth7 cg17233935 DSCR10 NM_148676 00233316 0.46 0.62 0.39 0.32 0.32 0.38 0.31 477/478 240 MOC_meth8 cg07376029 GC NM_000583 00145321 0.47 0.61 0.25 0.37 0.31 0.39 0.31 479/480 241 MOC_meth9 cg14893161 FLJ32569 NM_152491 00162877 0.36 0.59 0.35 0.22 0.40 0.30 0.25 481/482 242 MOC_meth10 cg24884084 SPRR1B NM_003125 00169469 0.45 0.57 0.39 0.43 0.24 0.41 483/484 243 MOC_meth11 cg12022621 LAX1 NM_017773 00122188 0.48 0.56 0.02 0.03 0.34 0.10 485/486 244 MOC_meth12 cg16399745 CNAP1 NM_014865 00010292 0.45 0.54 0.27 0.26 0.29 0.13 0.10 487/488 245 MOC_meth13 cg10117369 LAX1 NM_017773 00122188 0.46 0.53 0.02 0.05 0.43 0.15 489/490 246 MOC_meth14 cg24988345 SCHIP1 NM_014575 00250588 0.44 0.51 0.22 0.27 0.26 0.14 0.25 491/492 247 MOC_meth15 cg03427831 MTHFR NM_005957 00177000 0.36 0.50 0.27 0.25 0.24 0.13 0.08 493/494 248 MOC_meth16 cg05546044 MAPK1 NM_002745 00100030 0.30 0.50 0.15 0.18 0.16 0.12 495/496 249 GRC_nm1 cg22381196 DHODH NM_001361 00102967 0.05 0.72 0.89 0.84 0.78 0.78 0.87 497/498 250 GRC_nm2 cg06270401 DYRK4 NM_003845 00010219 0.06 0.80 0.84 0.82 0.79 0.81 0.75 499/500 251 GRC_nm3 cg22266967 S100P NM_005980 00163993 0.08 0.56 0.71 0.69 0.58 0.66 0.60 501/502 252 GRC_nm4 cg21283680 SH3BP5 NM_004844 00131370 0.12 0.60 0.77 0.72 0.61 0.64 0.74 503/504 253 GRC_nm5 cg20720686 POR NM_000941 00127948 0.15 0.52 0.80 0.77 0.76 0.74 0.74 505/506 254 GRC_nm6 cg12949760 KCNQ1 NT_009237 00053918 0.17 0.58 0.76 0.77 0.60 0.77 0.66 507/508 255 GRC_nm7 cg01718139 UNQ3033 NM_198481 00189068 0.18 0.72 0.78 0.72 0.78 0.78 0.74 509/510 256 GRC_nm8 cg05681757 FGD4 NM_139241 00139132 0.19 0.71 0.66 0.69 0.67 0.74 0.57 511/512 257 GRC_nm9 cg00145118 GNPDA1 NM_005471 00113552 0.19 0.51 0.60 0.67 0.58 0.62 0.74 513/514 258 GRC_nm10 cg10758292 DEFA1 NM_004084 00206047 0.20 0.90 0.76 0.75 0.78 0.83 0.75 515/516 259 nGRC_nm11 cg22438810 LCN2 NM_005564 00148346 0.20 0.81 0.74 0.72 0.65 0.60 0.64 517/518 260 GRC_nm12 cg02593766 EPN3 NM_017957 00049283 0.20 0.67 0.81 0.71 0.76 0.83 0.73 519/520 261 GRC_nm13 cg06625767 F12 NM_000505 00131187 0.21 0.65 0.87 0.87 0.86 0.86 0.89 521/522 262 GRC_nm14 cg18934187 STARD6 NM_139171 00174448 0.22 0.74 0.77 0.62 0.62 0.55 0.72 523/524 263 GRC_nm15 cg26306976 ITGB1BP1 NM_022334 00119185 0.22 0.92 0.90 0.87 0.81 0.87 0.72 525/526 264 GRC_nm16 cg09948350 FLJ25084 NM_152792 00244617 0.23 0.67 0.72 0.64 0.59 0.66 0.71 527/528 265 GRC_nm17 cg13265003 SLC37A1 NM_018964 00160190 0.24 0.75 0.81 0.81 0.69 0.79 0.74 529/530 266 GRC_nm18 cg25600606 HIPK3 NM_005734 00110422 0.25 0.86 0.91 0.84 0.77 0.89 0.88 531/532 267 GRC_nm19 cg12788313 MST1 NM_020998 00173531 0.26 0.64 0.92 0.93 0.82 0.89 533/534 268 GRC_nm20 cg17051440 CLDN2 NM_020384 00165376 0.27 0.61 0.79 0.77 0.68 0.57 0.71 535/536 269 GRC_nm21 cg24422489 FCGR2A NM_021642 00143226 0.27 0.68 0.80 0.73 0.68 0.70 0.81 537/538 270 GRC_nm22 cg15361231 GLRX2 NM_016066 00023572 0.27 0.64 0.83 0.75 0.62 0.67 0.77 539/540 271 GRC_nm23 cg10591659 NYX NM_022567 00188937 0.28 0.88 0.89 0.82 0.76 0.59 0.84 541/542 272 GRC_nm24 cg20098659 CLEC9A NM_207345 00197992 0.29 0.86 0.89 0.89 0.53 0.86 543/544 273 GRC_nm25 cg16504798 MYO1F NM_012335 00142347 0.30 0.56 0.88 0.79 0.77 0.69 545/546 274 GRC_nm26 cg15379858 ChGn NM_018371 00147408 0.31 0.92 0.93 0.93 0.93 0.94 0.87 547/548 275 GRC_nm27 cg07423149 CHI3L1 NM_001276 00133048 0.32 0.51 0.79 0.84 0.78 0.72 0.76 549/550 276 GRC_nm28 cg17823175 AZU1 NM_001700 00172232 0.35 0.52 0.85 0.85 0.85 0.87 0.83 551/552 277 GRC_nm29 cg21685427 SGK2 NM_016276 00101049 0.36 0.60 0.90 0.90 0.91 0.91 0.87 553/554 278 GRC_nm30 cg11849692 LDB1 NM_003893 00198728 0.36 0.71 0.60 0.79 0.57 0.89 555/556 279 GRC_nm31 cg22286764 C3orf35 NM_178339 00198590 037 0.81 0.94 0.95 0.67 0.95 557/558 280 GRC_nm32 cg18530324 KIAA0427 NM_014772 00134030 0.38 0.52 0.86 0.87 0.78 0.80 559/560 281 GRC_nm33 cg22630748 INHBE NM_031479 00139269 0.39 0.74 0.94 0.93 0.93 0.93 0.90 561/562 282 GRC_nm34 cg03311899 GPR109A NM_177551 00182782 0.43 0.54 0.95 0.93 0.92 0.91 0.95 563/564 283 GRC_nm35 cg00840516 HYAL2 NM_003773 00261921 0.43 0.75 0.91 0.88 0.89 0.84 565/566 284 GRC_nm36 cg02039171 CEBPE NM_001805 00092067 0.43 0.80 0.94 0.95 0.95 0.94 0.92 567/568 285 GRC_nm37 cg05826823 CIZ1 NM_012127 00148337 0.46 0.83 0.94 0.92 0.81 0.85 569/570 286 GRC_m1 cg02212836 LY86 NM_004271 00112799 0.90 0.14 0.08 0.14 0.07 0.42 571/572 287 GRC_m2 cg08136806 KRT6E NM_173086 00170465 0.65 0.48 0.32 0.39 0.41 0.39 0.27 573/574 288 GRC_m3 cg18959422 MYBPH NM_004997 00133055 0.64 0.41 0.41 0.48 0.37 0.42 0.34 575/576 289 GRC_m4 cg05106502 SCAP1 NM_003726 00141293 0.61 0.49 0.03 0.03 0.10 0.04 577/578 290 GRC_m5 cg10896774 C7orf34 NM_178829 00165131 0.55 0.45 0.18 0.22 0.23 0.38 0.12 579/580 291 GRC_m6 cg00323915 GIMAP4 NM_018326 00133574 0.55 0.42 0.17 0.28 0.43 0.20 0.19 581/582 292 GRC_m7 cg12605747 RPL4 NM_000968 00174444 0.54 0.41 0.36 0.33 0.31 0.26 0.34 583/584 293 GRC_m8 cg15625636 GPR65 NM_003608 00140030 0.54 0.32 0.12 0.20 0.29 0.31 0.25 585/586 294 GRC_m9 cg12810837 CLEC2D NM_001004419 00069493 0.52 0.45 0.11 0.15 0.18 0.14 0.16 587/588 295 GRC_m10 cg26839325 BMP15 NM_005448 00130385 0.52 0.45 0.24 0.24 0.24 0.27 0.18 589/590 296 eGRC_nm1 NA PRG2 00186652 NA NA NA NA NA NA NA 591/592 297 OTL_nm1 cg07728874 CD3D NM_000732.3 00167286 0.87 0.91 0.14 0.11 0.91 0.87 0.21 593/594 298 OTL_nm2 cg24841244 CD3D NM_000732.3 00167286 0.83 0.84 0.10 0.07 0.86 0.80 0.16 595/596 299 OTL_nm3 cg15880738 CD3G NM_000073.1 00160654 0.87 0.88 0.07 0.06 0.88 0.84 0.12 597/598 300 OTL_nm4 cg07545925 CD3G NM_000073.1 00160654 0.78 0.76 0.22 0.32 0.66 0.66 0.23 599/600 301 OTL_nm05 cg24612198 CD3E NM_000733.2 00198851 0.74 0.79 0.10 0.14 0.63 0.60 0.11 601/602 302 OTL_nm06 cg04759756 SLA2 NM_032214.2 00101082 0.91 0.91 0.21 0.12 0.91 0.73 0.20 603/604 303 OTL_nm07 cg08539991 ZBTB32 NM_014383.1 00011590 0.84 0.89 0.18 0.19 0.58 0.75 0.17 605/606 304 OTL_nm08 cg18350391 IL32 NM_001012631.1 00008517 0.82 0.87 0.15 0.13 0.82 0.68 0.18 607/608 305 OTL_nm09 cg19812619 ITGB7 NM_000889.1 00139626 0.90 0.90 0.29 0.25 0.63 0.71 0.28 609/610 306 OTL_nm10 cg20366831 APBA3 NM_004886.3 00011132 0.68 0.81 0.20 0.21 0.74 0.65 0.24 611/612 307 OTL_nm11 cg22670733 CHRNA3 NM_000743.2 00080644 0.78 0.82 0.22 0.22 0.82 0.80 0.45 613/614 308 OTL_nm12 cg16173109 FLJ38379 XR_001026.1 00204098 0.87 0.86 0.11 0.28 0.72 0.72 0.53 615/616 309 OTL_nm13 cg00620024 PPP6C NM_002721.3 00119414 0.86 0.85 0.18 0.28 0.69 0.74 0.44 617/618 310 OTL_nm14 cg15503752 ST6GALNA NM_018414.2 00070526 0.75 0.74 0.13 0.25 0.59 0.66 0.17 619/620 C1 311 OTL_nm15 cg15055101 SH2D3A NM_005490.1 00125731 0.77 0.82 0.19 0.34 0.72 0.70 0.48 621/622 312 OTL_nm16 cg18149207 RORC NM_005060.3 00143365 0.85 0.87 0.52 0.24 0.75 0.74 0.58 623/624 313 OTL_nm17 cg16854606 DAND5 NM_152654.2 00179284 0.66 0.77 0.34 0.31 0.79 0.65 0.27 625/626 314 OTL_m1 cg24091474 TYROBP NM_003332.2 00011600 0.12 0.08 0.84 0.84 0.27 0.10 0.60 627/628 315 OTL_m2 cg25957124 DNAH3 NM_017539.1 00158486 0.05 0.04 0.82 0.82 0.05 0.31 0.86 629/630 316 OTL_m3 cg01526089 P2RX1 NM_002558.2 00108405 0.03 0.04 0.86 0.84 0.52 0.32 0.85 631/632 317 OTL_m4 cg12971694 CD72 NM_001782.1 00137101 0.11 0.08 0.80 0.77 0.09 0.21 0.67 633/634 318 OTL_m5 cg19906550 SLC22A18 NM_183233.1 00110628 0.03 0.04 0.72 0.78 0.32 0.24 0.63 635/636 319 OTL_m6 cg17468997 NCF1 NM_000265.1 00158517 0.12 0.10 0.79 0.82 0.06 0.38 0.81 637/638 320 OTL_m7 cg19399532 FLJ35530 NM_207467.1 00204482 0.07 0.06 0.70 0.80 0.06 0.39 0.79 639/640 321 OTL_m8 cg09208010 MMP14 NM_004995.2 00157227 0.09 0.08 0.80 0.80 0.36 0.28 0.82 641/642 322 OTL_m9 cg15512851 FGD2 NM_173558.2 00146192 0.12 0.08 0.76 0.73 0.08 0.20 0.64 643/644 323 OTL_m10 cg20191453 AMT NM_000481.2 00145020 0.16 0.17 0.87 0.85 0.51 0.25 0.89 645/646 324 OTL_m11 cg24453664 CD59 NM_203331.1 00085063 0.07 0.10 0.79 0.79 0.37 0.29 0.82 647/648 325 OTL_m12 cg10257049 C5orf4 NM_032385.1 00170271 0.07 0.07 0.75 0.75 0.28 0.21 0.74 649/650 326 OTL_m13 cg16003913 MPG NM_001015052.1 00103152 0.05 0.15 0.82 0.81 0.41 0.32 0.82 651/652 327 OTL_m14 cg14088811 SPI1 NM_003120.1 00066336 0.10 0.07 0.77 0.74 0.08 0.41 0.79 653/654 328 OTL_m15 cg15146752 EPHA2 NM_004431.2 00142627 0.26 0.27 0.90 0.86 0.41 0.35 0.87 655/656 329 OTL_m16 cg02082571 CLEC4A NM_016184.2 00111729 0.23 0.14 0.85 0.87 0.44 0.47 0.83 657/658 330 OTL_m17 cg16989646 SLC25A15 NM_014252.1 00102743 0.04 0.07 0.69 0.59 0.04 0.11 0.54 659/660 331 OTL_m18 cg03574571 CD22 NM_001771.1 00012124 0.12 0.09 0.85 0.75 0.21 0.49 0.75 661/662 332 OTL_m19 cg13703437 FYB NM_199335.2 00082074 0.12 0.13 0.86 0.81 0.36 0.45 0.84 663/664 333 OTL_m20 cg21237418 RAB34 NM_031934.3 00109113 0.04 0.04 0.69 0.61 0.09 0.18 0.75 665/666 334 OTL_m21 cg01129847 C19orf35 NM_198532.1 00188305 0.08 0.12 0.69 0.62 0.18 0.06 0.53 667/668 335 OTL_m22 cg16139316 S100A9 NM_002965.2 00163220 0.06 0.07 0.84 0.73 0.49 0.37 0.85 669/670 336 OTL_m23 cg00666746 SYDE1 NM_033025.4 00105137 0.08 0.07 0.71 0.58 0.18 0.11 0.58 671/672 337 OTL_m24 cg20050826 K6IRS2 NM_080747.1 00170486 0.14 0.18 0.77 0.69 0.19 0.27 0.59 673/674 338 OTL_m25 cg12876594 NPR2 NM_000907.2 00139626 0.23 0.19 0.79 0.76 0.31 0.26 0.77 675/676 339 OTL_m26 cg17105014 GYPC NM_002101.3 00136732 0.13 0.14 0.76 0.70 0.35 0.26 0.68 677/678 340 OTL_m27 cg03886110 PECAM1 NM_000442.2 00261371 0.05 0.07 0.77 0.50 0.35 0.09 0.47 679/680 341 OTL_m28 cg14324675 LST1 NM_205838.1 00204482 0.05 0.04 0.63 0.71 0.24 0.36 0.65 681/682 342 OTL_m29 cg08519905 CD9 NM_001769.2 00010278 0.10 0.12 0.71 0.61 0.11 0.35 0.68 683/684

TABLE 4A Natural Killer Cells-Markers Basophil Marker- Target- Granu- ID ID SYMBOL Accession locytes NK_ cg2443 — — 0.97 nm33 0034 NK_ cg2727 ANKRD28 NM_ 0.92 nm34 4718 015199 NK_ cg0780 DNM3 NM_ 0.90 nm35 2362 015569 NK_ cg1329 CTBP2 NM_ 0.95 nm36 2607 001083914 NK_ cg0406 RHOBTB1 NM_ 0.91 nm37 4701 014836 NK_ cg0336 LDB2 NM_ 0.90 nm9 8758 001290 NK_ cg1789 LARP4B NM_ 0.97 nm39 3934 015155 NK_ cg1636 CXXC5 NM_ 0.87 nm40 0310 016463 NK_ cg2354 RNF165 NM_ 0.85 nm41 9472 152470 NK_ cg1362 EIF3G NM_ 0.94 nm42 0110 003755 NK_ cg2306 EIF2C2 NM_ 0.97 nm43 0465 012154 NK_ cg2127 MYO1E NM_ 0.88 nm44 5838 004998 NK_ cg1525 FAM120B NM_ 0.88 nm45 9233 032448 NK_ cg1179 — — 0.88 nm46 0417 NK_ cg0606 EIF3B NM_ 0.89 nm47 8163 001037283 NK_ cg1425 ADAM8 NM_ 0.89 nm48 9466 001109 NK_ cg1059 ZDHHC14 NM_ 0.90 nm49 2926 153746 NK_ cg0525 SLC15A4 NM_ 0.91 nm50 3716 145648 NK_ cg1716 RASA3 NM_ 0.92 nm51 2797 007368 NK_ cg0046 — — 0.94 nm52 2849 NK_ cg1005 C1GALT1 NM_ 0.91 nm53 5950 020156 NK_ cg1991 COLQ NM_ 0.86 nm54 5997 080538 NK_ cg0670 MAST3 NM_ 0.97 nm55 6159 015016 NK_ cg2301 MAD1L1 NM_ 0.92 nm56 5664 003550 NK_ cg2182 RFC2 NM_ 0.69 nm57 8319 181471 NK_ cg0542 AKAP10 NM_ 0.75 nm58 1487 007202 NK_ cg2446 SBNO2 NM_ 0.84 nm59 7387 014963 NKT_ cg0558 — — 0.89 nm21 5475 NKT_ cg2006 PDGFA NM_ 0.91 nm22 3728 002607 NKT_ cg0087 C14orf NM_ 0.91 nm23 9541 166 016039 NKT_ cg2621 — — 0.92 nm24 5982 NKT_ cg0845 TBC1D22B NM_ 0.85 nm25 5089 017772 NKT_ cg0904 — — 0.87 nm26 6550 NKT_ cg2731  LDHAL6A NM_ 0.89 nm27 6453 001144071 NKT_ cg0306 ST7 NM_ 0.90 nm28 9731 018412 NKT_ cg2364 — — 0.89 nm29 2827 NKT_ cg1221  ZAK NM_ 0.88 nm30 9570 016653 NKT_ cg1654 — — 0.89 nm3l 8262 NKT_ cg0584 NCRNA NR_ 0.87 nm32 4859 00119 002811 NKT_ cg1574 TBC1D23 NM_ 0.88 nm33 0507 018309 NKT_ cg0740 — — 0.84 nm34 6728 NKT_ cg1399  SAMD4A NM_ 0.82 nm35 4599 001161577 NKT_ cg0334 GCK NM_ 0.84 nm36 5391 000162 NKT_ cg0789 PTK2 NM_ 0.91 nm37 1862 153831 NKT_ cg2550 AOAH NM_ 0.87 nm38 3323 001637 NKT_ cg2403 C3orf30 NM_ 0.90 nm39 7746 152539 NKT_ cg1338 SGMS1 NM_  0.88 nm40 2516 147156 NKT_ cg2591 — — 0.85 nm41 8166 NKT_ cg0825 — — 0.90 nm42 0738 NKT_ cg1908 RCAN2 NM_ 0.86 nm43 3007 005822 NKT_ cg0622 ELFN1 NM_001 0.80 nm44 8763 128636 NKT_ cg1924 UBE2E2 NM_ 0.82 nm45 3780 152653 NKT_ cg1157 CLIP1 NM_ 0.89 nm46 1124 002956 NKT_ cg1756 — — 0.89 nm47 9413 NKT_ cg1408 KCNQI NM_ 0.86 nm48 9425 000218 NKT_ cg2689 GPR89A NM_ 0.85 nm49 4807 001097613 NKT_ cg0279 OSBPL10 NM_ 0.86 nm50 1542 017784 NKT_ cg2458 IL9 NM_ 0.86 nm51 5690 000590 NKT_ cg1890 TNKS2 NM_ 0.87 nm52 4552 025235 NKT_ cg1807 — — 0.88 nm53 7068 NKT_ cg0390 KCNQ1 NM_ 0.83 nm54 5757 000218 NKT_ cg1263 — — 0.91 nm55 0243 NKT_ cg1239 — — 0.83 nm56 9350 NKT_ cg0082 — — 0.86 nm57 9600 NKT_ cg2472 PLEKHA7 NM_ 0.86 nm58 2886 175058 NKT_ cg1656 — — 0.87 nm59 5562 NKT_ cg1336 — — 0.79 nm60 2028 Eosino- Neutro- sinophil phil Non- Marker- Granu- Granu- Classical Classical ID locytes locytes Monocytes Monocytes NK_ 0.97 0.97 0.97 0.95 nm33 NK_ 0.89 0.91 0.91 0.87 nm34 NK_ 0.91 0.92 0.92 0.90 nm35 NK_ 0.91 0.92 0.93 0.92 nm36 NK_ 0.90 0.93 0.93 0.91 nm37 NK_ 0.85 0.88 0.88 0.86 nm9 NK_ 0.96 0.96 0.96 0.96 nm39 NK_ 0.82 0.85 0.87 0.84 nm40 NK_ 0.86 0.87 0.88 0.88 nm41 NK_ 0.91 0.92 0.92 0.93 nm42 NK_ 0.97 0.97 0.97 0.96 nm43 NK_ 0.90 0.89 0.89 0.89 nm44 NK_ 0.86 0.88 0.89 0.87 nm45 NK_ 0.90 0.88 0.89 0.89 nm46 NK_ 0.87 0.90 0.90 0.87 nm47 NK_ 0.71 0.96 0.96 0.93 nm48 NK_ 0.94 0.95 0.95 0.92 nm49 NK_ 0.91 0.92 0.93 0.89 nm50 NK_ 0.91 0.92 0.94 0.92 nm51 NK_ 0.94 0.95 0.94 0.92 nm52 NK_ 0.92 0.92 0.91 0.89 nm53 NK_ 0.87 0.88 0.88 0.87 nm54 NK_ 0.97 0.98 0.97 0.94 nm55 NK_ 0.94 0.96  0.94 0.94 nm56 NK_ 0.92 0.92 0.91 0.90 nm57 NK_ 0.85 0.90 0.90 0.89 nm58 NK_ 0.91 0.93 0.92 0.88 nm59 NKT_ 0.86 0.89 0.90 0.90 nm21 NKT_ 6.89 0.89 0.91 0.90 nm22 NKT_ 0.90 0.89 0.90 0.84 nm23 NKT_ 0.91 0.90 0.90 0.91 nm24 NKT_ 0.84 0.90 0.88 0.84 nm25 NKT_ 0.89 0.87 0.89 0.88 nm26 NKT_ 0.90 0.90 0.88 0.86 nm27 NKT_ 0.86 0.86 0.87 0.87 nm28 NKT_ 0.92 0.90 0.91 0.90 nm29 NKT_ 0.87 0.91 0.93 0.91 nm30 NKT_ 0.79 0.80 0.84 0.84 nm3l NKT_ 0.90 0.88 0.87 0.87 nm32 NKT_ 0.79 0.86 0.82 0.76 nm33 NKT_ 0.85 0.89 0.87 0.83 nm34 NKT_ 0.80 0.81 0.81 0.82 nm35 NKT_ 0.86 0.87 0.82 0.83 nm36 NKT_ 0.91 0.90 0.91 0.87 nm37 NKT_ 0.88 0.84 0.88 0.89 nm38 NKT_ 0.90 0.90 0.88 0.87 nm39 NKT_ 0.86 0.89 0.89 0.89 nm40 NKT_ 0.84 0.85 0.84 0.83 nm41 NKT_ 0.92 0.92 0.93 0.93 nm42 NKT_ 0.85 0.86 0.87 0.85 nm43 NKT_ 0.76 0.77 0.80 0.78 nm44 NKT_ 0.82 0.85 0.89 0.84 nm45 NKT_ 0.88 0.90 0.89 0.88 nm46 NKT_ 0.88 0.89 0.88 0.89 nm47 NKT_ 0.87 0.89 0.90 0.86 nm48 NKT_ 0.89 0.89 0.89 0.90 nm49 NKT_ 0.86 0.85 0.86 0.84 nm50 NKT_ 0.85 0.87 0.87 0.87 nm51 NKT_ 0.82 0.89 0.90 0.89 nm52 NKT_ 0.87 0.89 0.85 0.86 nm53 NKT_ 0.86 0.86 0.85 0.84 nm54 NKT_ 0.86 0.88 0.91 0.91 nm55 NKT_ 0.80 0.81 0.86 0.86 nm56 NKT_ 0.83 0.79 0.87 0.88 nm57 NKT_ 0.81 0.84 0.83 0.85 nm58 NKT_ 0.83 0.84 0.87 0.87 nm59 NKT_ 0.78 0.76 0.76 0.77 nm60 Marker- NK CD4 + Th ID classical B-Cells naive CD4 + Th1 NK_ 0.09 0.97 0.97 0.97 nm33 NK_ 0.08 0.90 0.92 0.90 nm34 NK_ 0.12 0.90 0.91 0.86 nm35 NK_ 0.16 0.93 0.94 0.89 nm36 NK_ 0.16 0.92 0.91 0.91 nm37 NK_ 0.16 0.88 0.89 0.93 nm9 NK_ 0.22 0.97 0.97 0.95 nm39 NK_ 0.15 0.86 0.85 0.86 nm40 NK_ 0.18 0.92 0.84 0.86 nm41 NK_ 0.27 0.94 0.94 0.91 nm42 NK_ 0.33 0.97 0.97 0.97 nm43 NK_ 0.27 0.86 0.88 0.90 nm44 NK_ 0.30 0.89 0.89 0.87 nm45 NK_ 0.31 0.88 0.88 0.85 nm46 NK_ 0.33 0.89 0.90 0.87 nm47 NK_ 0.17 0.93 0.87 0.96 nm48 NK_ 0.22 0.93 0.86 0.91 nm49 NK_ 0.22 0.91 0.92 0.91 nm50 NK_ 0.31 0.91 0.92 0.91 nm51 NK_ 0.35 0.94 0.95 0.93 nm52 NK_ 0.13 0.90 0.92 0.92 nm53 NK_ 0.07 0.87 0.86 0.81 nm54 NK_ 0.19 0.98 0.98 0.98 nm55 NK_ 0.04 0.95 0.93 0.95 nm56 NK_ 0.08 0.74 0.67 0.91  nm57 NK_ 0.21 0.90 0.76 0.86 nm58 NK_ 0.23 0.91 0.83 0.88 nm59 NKT_ 0.83 0.81 0.90 0.81 nm21 NKT_ 0.85 0.89 0.90 0.69 nm22 NKT_ 0.87 0.84 0.87 0.72 nm23 NKT_ 0.83 0.81 0.89 0.59 nm24 NKT_ 0.86 0.81 0.84 0.51 nm25 NKT_ 0.83 0.87 0.88 0.51 nm26 NKT_ 0.80 0.82 0.91 0.55 nm27 NKT_ 0.84 0.82 0.87 0.56 nm28 NKT_ 0.82 0.80 0.91 0.60 nm29 NKT_ 0.83 0.82 0.88 0.57 nm30 NKT_ 0.79 0.82 0.90 0.61 nm3l NKT_ 0.82 0.80 0.86 0.55 nm32 NKT_ 0.77 0.80 0.88 0.59 nm33 NKT_ 0.83 0.86 0.85 0.57 nm34 NKT_ 0.81 0.80 0.87 0.54 nm35 NKT_ 0.82 0.80 0.85 0.57 nm36 NKT_ 0.84 0.81 0.88 0.58 nm37 NKT_ 0.83 0.87 0.88 0.50 nm38 NKT_ 0.73 0.83 0.89 0.60 nm39 NKT_ 0.79 0.75 0.88 0.67 nm40 NKT_ 0.80  0.78 0.84 0.48 nm41 NKT_ 0.86 0.78 0.89 0.62 nm42 NKT_ 0.84 0.77 0.87 0.49 nm43 NKT_ 0.75 0.74 0.81 0.49 nm44 NKT_ 0.83 0.87 0.84 0.46 nm45 NKT_ 0.72 0.83 0.87 0.51 nm46 NKT_ 0.90 0.83 0.91 0.53 nm47 NKT_ 0.80 0.76 0.85 0.57 nm48 NKT_ 0.85 0.80 0.87 0.57 nm49 NKT_ 0.77 0.82 0.87 0.49 nm50 NKT_ 0.85 0.78 0.88 0.62 nm51 NKT_ 0.88 0.89 0.88 0.50 nm52 NKT_ 0.84 0.77 0.87 0.51 nm53 NKT_ 0.77 0.79 0.84 0.58 nm54 NKT_ 0.84 0.77 0.89 0.51 nm55 NKT_ 0.73 0.79 0.82 0.54 nm56 NKT_ 0.79 0.84 0.84 0.49 nm57 NKT_ 0.75 0.81 0.82 0.55 nm58 NKT_ 0.81 0.76 0.85 0.48 nm59 NKT_ 0.74 0.73 0.73 0.47 nm60 CD4 + CD4 + CD8 + Th Th Cyto- Marker- CD4 + Central Effect. toxic ID Th2 Mem. Mem. T-Cells NK_ 0.97 0.96 0.95 0.93 nm33 NK_ 0.91 0.91 0.92 0.89 nm34 NK_ 0.87 0.90 0.90 0.83 nm35 NK_ 0.89 0.91 0.91 0.87 nm36 NK_ 0.92 0.91 0.91 0.89 nm37 NK_ 0.91 0.93 0.93 0.91 nm9 NK_ 0.96 0.96 0.96 0.93 nm39 NK_ 0.87 0.86 0.86 0.87 nm40 NK_ 0.85 0.87 0.86 0.83 nm41 NK_ 0.90 0.95 0.94 0.93 nm42 NK_ 0.97 0.97 0.97 0.94 nm43 NK_ 0.90 0.90 0.89 0.90 nm44 NK_ 0.86 0.87 0.89 0.90 nm45 NK_ 0.87 0.89 0.87 0.89 nm46 NK_ 0.86 0.87 0.89 0.89 nm47 NK_ 0.96 0.96 0.96 0.96 nm48 NK_ 0.92 0.94 0.93 0.91 nm49 NK_ 0.91 0.91 0.92 0.91 nm50 NK_ 0.93 0.92 0.92 0.93 nm51 NK_ 0.92 0.94 0.94 0.95 nm52 NK_ 0.92 0.93 0.89 0.91 nm53 NK_ 0.82 0.85 0.83 0.82 nm54 NK_ 0.98 0.98 0.98 0.88 nm55 NK_ 0.95 0.94 0.96 0.92 nm56 NK_ 0.92 0.92 0.92 0.90 nm57 NK_ 0.88 0.89 0.90 0.85 nm58 NK_ 0.90 0.93 0.90 0.88 nm59 NKT_ 0.83 0.86 0.86 0.67 nm21 NKT_ 0.85 0.82 0.79 0.63 nm22 NKT_ 0.80 0.81 0.77 0.70 nm23 NKT_ 0.70 0.74 0.67 0.59 nm24 NKT_ 0.62 0.61 0.48 0.60 nm25 NKT_ 0.70 0.63 0.60 0.69 nm26 NKT_ 0.65 0.68 0.60 0.69 nm27 NKT_ 0.70 0.67 0.61 0.68 nm28 NKT_ 0.79 0.77 0.74 0.59 nm29 NKT_ 0.61 0.67 0.60 0.68 nm30 NKT_ 0.79 0.71 0.71 0.68 nm3l NKT_ 0.54 0.66 0.59 0.68 nm32 NKT_ 0.74 0.68 0.61 0.66 nm33 NKT_ 0.67 0.68 0.64 0.68 nm34 NKT_ 0.57 0.66 0.62 0.67 nm35 NKT_ 0.58 0.70 0.61 0.69 nm36 NKT_ 0.67 0.72 0.62 0.66 nm37 NKT_ 0.61 0.67 0.60 0.61 nm38 NKT_ 0.76 0.75 0.71 0.66 nm39 NKT_ 0.74 0.72 0.69 0.61 nm40 NKT_ 0.60 0.68 0.59 0.58 nm41 NKT_ 0.70 0.71 0.68 0.63 nm42 NKT_ 0.59 0.64 0.60 0.65 nm43 NKT_ 0.51 0.51 0.45 0.52 nm44 NKT_ 0.50 0.63 0.54 0.69 nm45 NKT_ 0.62 0.60 0.56 0.66 nm46 NKT_ 0.70 0.63 0.59 0.70 nm47 NKT_ 0.70 0.75 0.70 0.70 nm48 NKT_ 0.47 0.64 0.63 0.61 nm49 NKT_ 0.53 0.61 0.56 0.61 nm50 NKT_ 0.59 0.68 0.67 0.67 nm51 NKT_ 0.62 0.58 0.53 0.74 nm52 NKT_ 0.56 0.63 0.52 0.69 nm53 NKT_ 0.66 0.73 0.68 0.62 nm54 NKT_ 0.57 0.66 0.61 0.69 nm55 NKT_ 0.65 0.62 0.58 0.64 nm56 NKT_ 0.55 0.60 0.55 0.61 nm57 NKT_ 0.57 0.66 0.61 0.59 nm58 NKT_ 0.52 0.64 0.59 0.67 nm59 NKT_ 0.51 0.55 0.44 0.61 nm60 Marker- ID NK T-Cells Discovery Fragment NK_ 0.80 CGCTCCCCAAGTGCTGA nm33 CCACGCGCGCCCCCACG GCTCCCCGACAGCTCC NK_ 0.87 AGTAGGTAAAAACACTG nm34 ATGCACTCTGCTTACCA TGTAAGCCTCTTAACG NK_ 0.83 CGGCTCCAAATCAAAAG nm35 CTGTGGAAGGAGGTAAT TAGCAGGGACTCTAGA NK_ 0.85 TTTTGTTGGTTCCTCACG nm36 TGGGCAGAAGAGTGAA TGCTCAGTCCCCATCG NK_ 0.84 AGCTGATACTGCGTGAG nm37 TGTGGTGTTGCACGCCC TGGCACAGATCAAGCG NK_ 0.90 CCCTTCACAACCTGATT nm9 GCTAAGCTTGTTAGCAT AGAGGTGGTCTAACCG NK_ 0.87 AAAACCGTACGTCTGGG nm39 AGGGGTCGCAGAGCGCT GTGTTAACCACAAACG NK_ 0.84 CCATTACCACTGGCTTT nm40 GTTACAATCTATTACAA CAATAGCAGTTGGCCG NK_ 0.84 CGGAAGGGCAACAGAA nm41 CAAAAGCAGCGTACAAT GAGCAGATGGCCCGGGC NK_ 0.87 GGGGATAATTACGAGGT nm42 GCCGGGAGGTGCCCACC CACCAGCCTGGCGTCG NK_ 0.93 CAGAGGGCTCTGAGCGG nm43 GCTGTGTGCCGGGCGAG AACACTGCCTGGGCCG NK_ 0.87 CGCAGCTTATTTGTCAC nm44 TGAGAAAGTTCAAGTTA GTGCTCTAATTCCACC NK_ 0.85 CGGGGCAGCTGCCTGCA nm45 CTGAGCTCTGAGGCCTT TGAAGTGGACCAGAGA NK_ 0.85 TTAAGGGCCAACCCTGA nm46 CCACAGCTGAGCCGTGT GAAGAGGCTGACAGCG NK_ 0.88 CGGCTACAAGCTTGACA nm47 AGCAGCACACATTCCGG GTCAACCTCTTTACGG NK_ 0.92 CGGCGTCTCCAGGCCTG nm48 CGGCCAAGCGTGCTTGC CCTTGGTGACCACATT NK_ 0.92 GGCGCTCTGCCTGCAGC nm49 TATCTCCGTGTCAATGG CATCCTTTGATAGTCG NK_ 0.79 CGCCAGAGTAATGGGTA nm50 AGCACTTAGTTCTCATC TTGGGCTGTTTGAAAG NK_ 0.91 CGCTAAACGGTGCCACA nm51 GTTTTACTCTCTTGGAA CTGTCCCACATGGGTT NK_ 0.92 CGAGGCATCGGCCCGTT nm52 TTGTGTCTGGTAAGGGC CAGAGTCCTGGTTCAT NK_ 0.81 CGCTCACTGCTTACTTA nm53 AATGGACAGTTTTAAGT TTCAGTTTTAAGCTCA NK_ 0.73 CGTGCAGGCATTCTCAC nm54 TCACACTGGGCAGCCCG CTGTCGGGTCTCTCTA NK_ 0.70 CGAGCTCGGCCTCTGGC nm55 CCACGAGTGCGCCGCCC CGCCTCCCCATCCAGC NK_ 0.80 CGCGGACCCCGCTTCTG nm56 TCACCCCTAACCTCACT GTTGGGTCCGGGACCT NK_ 0.84 CGGGGCACAGACGTCCC nm57 AGAAGCAAACATGCAA GTCACGGGAGTTTATTT NK_ 0.83 TCTATATCTGATCCATC nm58 AGCAAATCTGTTAGGTC TACCTCACACATATCG NK_ 0.82 GTGGGTCTCACTCAGCT nm59 GGGCGCTGGGGCCCTGG TGGAGAATGGCTGTCG NKT_ 0.27 CGGTAGACAAATGATAG nm21 ACATTTGTTGAATCAAG CTGTGAGTTGGAGATC NKT_ 0.13 GTCTTTGCCTGACACCT nm22 TCTGTGAGGTTTGCGGG CTTCATTTTAAATCCG NKT_ 0.17 GGGGTTATATATTTTTG  nm23 ACCAAATTCACCATTAC TCATTTGGCATTTTCG NKT_ 0.15 GCGTACACACCCTGATA nm24 AGGTGTCAAGAACCTCC GTTTGAGTACCCCTCG NKT_ 0.15 CCTGCTGTAGATGTGTC nm25 ACAGCTAAATTCTTGAA TGGATTTTTATCATCG NKT_ 0.22 GAACCAAGCACTGCTTC nm26 CTGGGAGAGTGATGMA GCATGACTCAAAGGCG NKT_ 0.23 CGCAAACCCACCCTCTA nm27 TCCGGGTGAGCACCATC TAGTCAGCTGCCAGCA NKT_ 0.24 CGTGGGATCTCTGTTCA nm28 TTTTGGTATATTACTTTG CTTTCTGGGCTGAGC NKT_ 0.26 CGCATACTTTCAGGGAG nm29 AGGCACTATTCTTGGCT TTAAGTTCATGAGTAA NKT_ 0.25 CGGGGGGAGAATTAAG nm30 CCAAAGAAGTATATTTA TGAATCAGCAAATGTGG NKT_ 0.24 CGGCTTGAACCCTCAGC nm3l TTCTACAGTTGTGTCAC CCATGTGTCTGTTTCT NKT_ 0.24 GGCCGAGGTGAAACCAT nm32 TGGTTTTTAACCTTGACT ACTGATTAAAATCCG NKT_ 0.24 ATCAGCACCAAAGCTTT nm33 GTCTGAACTTATTTTGCT ACTATTGTTAGGACG NKT_ 0.27 CGACTGTGGGGAATGAA nm34 TAAGATTACAATAAAAC CTGAGGAATTTAATGC NKT_ 0.26 CGAGTGAGTCCAAACTC nm35 CTTAGAAAGTTGGTTGC TAAGGACTTGGAAAAG NKT_ 0.28 CCCTTCCCCAAGTTCCA nm36 TACAGACCCCTGGATTG TATGAAATGCAAATCG NKT_ 0.14 CGGAGAGCAAACAGGG nm37 CTAACACAGAAAGCCCT TGTAAAAAACAGAACGA NKT_ 0.15 CGAGGAAGGTATGGTA nm38 GAAATGCATCCATTACC AAGAAGAAAAGTAATCT NKT_ 0.20 CACATCACTATATGGAA nm39 CACGACTATACTTTCAA AAGATGACCAATCTCG NKT_ 0.20 CGTGCCCAGCTTTTCTA nm40 TGGGAAAAATTGTTCTT CAGACAGAGCATGAAT NKT_ 0.17 CGTCATTATCTGGCAAT nm41 AGTTGTTGGATGTGTTT GCTGCCATGCCACGAG NKT_ 0.26 CGTAGGTTTCCAAGAAA nm42 GATAGGGTGACAAAATT GCCTGTCACTCCGATT NKT_ 0.21 CGGATTTCTATTCAGCC nm43 CATGCCCGGGATGCATT AGGATGCCCAGAACAT NKT_ 0.14 GGGAGTGGCCCAGCCCG nm44 GTTTGCTCAGTGACCAG GATGTTTCCACAGTCG NKT_ 0.21 GTGCTCTGGTTACATCA nm45 GCAAACATGTTCTACAA TCAAGGTAAAAACTCG NKT_ 0.23 CGAGTACTAAAAGGTCA nm46 AATGTGTCAAGTCTAGA ACTAGTACTCTTTTTT NKT_ 0.26 CGCACCATCACACCGTC nm47 AGCAACTTGTGGGACCA ACTCCCTGCACATCTG NKT_ 0.25 AGTACATCTGTTGACAA nm48 CATGGTTTACTGAATAT GTTGAGCCCATTTTCG NKT_ 0.23 TCTATCTTCATTTAACTT nm49 CCAGTCCTTTGCCCTAC AGATAATTCGTAGCG NKT_ 0.21 CGGCCAAAAGAAAGAC nm50 ATAGAATAGAATGGTGG TTGCTGAGGGTTGGAGA NKT_ 0.24 CGGACTGGAGCTCGCTT nm51 GCAGACACCTTCAAATC GAGTGGTATTTAAAGC NKT_ 0.27 ACAAACAAAAAGCTATC nm52 TGAAAATGCTGCCATGC TAACATATGAACCACG NKT_ 0.26 CGAATGGAAATTCAAAG nm53 GGAGAACATCTAATGTT CAAGTTGATGTCTATA NKT_ 0.26 CGTCCCCTCTAATACTA nm54 TAGCTGAGAGCTTTTAA TATGAATGGGTGTTAA NKT_ 0.28 CGACTGGTGTTGATTCT nm55 CAGTCAATTTAAAGGAT GAAAAGGGCTGTAAAA NKT_ 0.25 CCCAGTTCTTCAGAGTT nm56 GTCAGGGTCACTGCTCT GGGACCCACGGACTCG NKT_ 0.26 CGAAGGAGGGAGTGCA nm57 TGAATTCATGTAAGGAT GGAGATCCACATCCCAG NKT_ 0.26 CGAGTGTGGAGCTATGA nm58 TTGGAACCTAGTTCAGG CTCCAAAGCCACACTC NKT_ 0.28 CGGATTTTTGAGACAGT nm59 TTGGGAATAGTTTATCC TGTTATTATCTTCAGG NKT_ 0.24 CGTTAGGATTGCTAAAG nm60 GCATTTTCTAAATATT TGAGTGTAAACCACTG

TABLE 4B B-Cell Markers Basophil Marker- Target- Granu- ID ID SYMBOL Accession locytes B_ cg2290  CYBASC3 NM_ 0.88 nm45 7103 153611 B_ cg1553 NFATC1 NM_ 0.87 nm46 2942 006162 B_ cg2710 NFATC1 NM_ 0.89 nm47 6643 006162 B_ cg0784 TTLL10 NM_ 0.92 nm48 1371 001130045 B_ cg1373 LRP5 NM_ 0.98 nm49 8327 002335 B_ cg2655 — — 0.87 nm50 2743 B_ cg0520 — — 0.92 nm51 5074 B_ cg0772 LOC1001 NR_ 0.94 nm52 1872 29637 024488 B_ cg1166 UBE2O NM_ 0.90 nm53 1493 022066 B_ cg0221 TRPV1 NM_ 0.98 nm54 2339 080704 B_ cg2756 CD19 NM_ 0.91 nm55 5966 001770 B_ cg2546 — — 0.85 nm56 9923 B_ cg2249 TBCD NM_ 0.86 nm57 8365 005993 B_ cg1723 SORL1 NM_ 0.89 nm58 2476 003105 B_ cg1866 C7orf50 NM_ 0.88 nm59 4915 001134395 B_ cg2060 C15orf57 NM_ 0.91 nm60 2300 052849 B_ cg1825 TERF1 NM_ 0.89 nm61 0453 003218 B_ cg0688 — — 0.90 nm62 9975 B_ cg1169 BAHCC1 NM_ 0.99 nm63 9517 001080519 B_ cg1503 LRIG1 NM_ 0.91 nm64 5590 015541 B_ cg1524 MICAL3 NM_ 0.88 nm65 2630 001122731 B_ cg1382 — — 0.88 nm66 3257 B_ cg1391 CDK19 NM_ 0.88 nm67 5752 015076 B_ cg0483 GOLSYN NM_ 0.98 nm68 8847 001099743 B_ cg2228 INPP5J NM_ 0.88 nm69 1206 001002837 B_ cg1926 — — 0.87 nm70 0718 B_ cg1976 EIF3G NM_ 0.89 nm71 6988 003755 B_ cg2045 ITPKB NM_ 0.90 nm72 2738 002221 B_ cg2669 IQSEC1 NM_ 0.95 nm73 2003 300114382 B_ cg0076 IRF2 NM_ 0.92 nm74 2029 002199 B_ cg1762 ZDHHC14 NM_ 0.87 nm75 2855 153746 B_ cg0494  WDFY4 NM_ 0.88 nm76 7949 020945 B_ cg2513 — — 0.96 nm77 1632 B_ cg1448 LCN8 NM_ 0.93 nm78 2811 178469 B_ cg1217 PLXND1 NM_ 0.96 nm79 7944 015103 B_ cg2124 C7orf50 NM_ 0.96 nm80 8060 001134395 B_ cg0482 CARS2 NM_ 0.95 nm81 8493 024537 B_ cg0102 RERE NM_ 0.91 nm82 4458 012102 B_ cg2568 HVCN1 NM_ 0.92 nm83 3989 001040107 B_ cg2221 FRMD8 NM_ 0.89 nm84 2560 031904 B_ cg1534 — — 0.77 nm85 8679 B_ cg1621 CGNL1 NM_ 0.92 nm86 0395 032866 B_ cg0816 IQSEC1 NM_ 0.91 nm87 2476 001134382 B_ cg0759 CD19 NM_ 0.86 nm15 7976 001770 B_ cg0776 RNF44 NM_ 0.98 nm89 8103 014901 B_ cg1335 ATP10A NM_ 0.91 nm90 6455 902440 B_ cg1799 LHPP NM_ 0.87 nm91 5557 022126 B_ cg1767 — — 0.90 nm92 9619 B_ cg2730 CD84 NM_ 0.89 nm93 4328 003874 B_ cg2643 CD81 NM_ 0.89 nm94 8284 004356 Eosino- Neutro- sinophil phil Non- Marker- Granu- Granu- Classical Classical ID locytes locytes Monocytes Monocytes B_ 0.87 0.86 0.84 0.83 nm45 B_ 0.91 0.88 0.91 0.89 nm46 B_ 0.92 0.93 0.90 0.87 nm47 B_ 0.94 0.94 0.95 0.92 nm48 B_ 0.98 0.98 0.98 0.97 nm49 B_ 0.84 0.86 0.89 0.85 nm50 B_ 0.92 0.93 0.92 0.88 nm51 B_ 0.95 0.93 0.96 0.95 nm52 B_ 0.88 0.89 0.90 0.87 nm53 B_ 0.97 0.97 0.97 0.96 nm54 B_ 0.89 0.91 0.91 0.89 nm55 B_ 0.86 0.87 0.86 0.83 nm56 B_ 0.91 0.92 0.90 0.86 nm57 B_ 0.90 0.89 0.86 0.83 nm58 B_ 0.90 0.88 0.89 0.87 nm59 B_ 0.90 0.92 0.91 0.90 nm60 B_ 0.85 0.90 0.91 0.90 nm61 B_ 0.84 0.85 0.87 0.89 nm62 B_ 0.97 0.97 0.97 0.97 nm63 B_ 0.91 0.90 0.92 0.89 nm64 B_ 0.88 0.87 0.87 0.85 nm65 B_ 0.88 0.89 0.88 0.86 nm66 B_ 0.85 0.90 0.90 0.90 nm67 B_ 0.98 0.98 0.97 0.98 nm68 B_ 0.89 0.90 0.88 0.85 nm69 B_ 0.90 0.89 0.90 0.86 nm70 B_ 0.90 0.89 0.90 0.85 nm71 B_ 0.89 0.91 0.88 0.90 nm72 B_ 0.96 0.97 0.95 0.91 nm73 B_ 0.91 0.92 0.92 0.90 nm74 B_ 0.88 0.89 0.89 0.89 nm75 B_ 0.91 0.92 0.91 0.89 nm76 B_ 0.97 0.97 0.97 0.96 nm77 B_ 0.92 0.96 0.95 0.95 nm78 B_ 0.96 0.94 0.86 0.68 nm79 B_ 0.96 0.97 0.97 0.95 nm80 B_ 0.96 0.95 0.86 0.73 nm81 B_ 0.92 0.93 0.92 0.93 nm82 B_ 0.77 0.92 0.92 0.91 nm83 B_ 0.86 0.90 0.72 0.62 nm84 B_ 0.83 0.88 0.87 0.86 nm85 B_ 0.92 0.93 0.94 0.93 nm86 B_ 0.92 0.91 0.78 0.74 nm87 B_ 0.82 0.82 0.82 0.78 nm15 B_ 0.98 0.98 0.98 0.98 nm89 B_ 0.89 0.90 0.90 0.90 nm90 B_ 0.90 0.87 0.89 0.87 nm91 B_ 0.85 0.89 0.89 0.88 nm92 B_ 0.61 0.84 0.84 0.83 nm93 B_ 0.84 0.87 0.89 0.88 nm94 Marker- NK CD4 + Th ID classical B-Cells naive CD4 + Th1 B_ 0.86 0.04 0.87 0.85 nm45 B_ 0.89 0.07 0.87 0.86 nm46 B_ 0.90 0.11 0.90 0.90 nm47 B_ 0.95 0.10 0.94 0.94 nm48 B_ 0.97 0.03 0.97 0.93 nm49 B_ 0.89 0.04 0.86 0.86 nm50 B_ 0.91 0.04 0.92 0.86 nm51 B_ 0.93 0.03 0.93 0.94 nm52 B_ 0.91 0.04 0.89 0.89 nm53 B_ 0.97 0.05 0.97 0.95 nm54 B_ 0.84 0.06 0.90 0.91 nm55 B_ 0.82 0.06 0.89 0.85 nm56 B_ 0.91 0.07 0.88 0.89 nm57 B_ 0.89 0.07 0.89 0.87 nm58 B_ 0.88 0.07 0.90 0.86 nm59 B_ 0.91 0.07 0.90 0.89 nm60 B_ 0.82 0.08 0.89 0.88 nm61 B_ 0.90 0.08 0.89 0.90 nm62 B_ 0.99 0.08 0.98 0.98 nm63 B_ 0.88 0.09 0.92 0.92 nm64 B_ 0.88 0.09 0.88 0.86 nm65 B_ 0.89 0.09 0.88 0.85 nm66 B_ 0.91 0.10 0.89 0.90 nm67 B_ 0.98 0.10 0.98 0.98 nm68 B_ 0.89 0.10 0.89 0.88 nm69 B_ 0.89 0.11 0.87 0.88 nm70 B_ 0.89 0.11 0.89 0.87 nm71 B_ 0.90 0.11 0.91 0.88 nm72 B_ 0.96 0.12 0.97 0.96 nm73 B_ 0.93 0.13 0.92 0.91 nm74 B_ 0.87 0.13 0.88 0.85 nm75 B_ 0.88 0.13 0.90 0.89 nm76 B_ 0.96 0.03 0.97 0.90 nm77 B_ 0.70 0.04 0.90 0.96 nm78 B_ 0.97 0.05 0.97 0.93 nm79 B_ 0.95 0.10 0.97 0.96 nm80 B_ 0.85 0.05 0.96 0.92 nm81 B_ 0.91 0.03 0.92 0.76 nm82 B_ 0.89 0.06 0.91 0.89 nm83 B_ 0.93 0.03 0.90 0.91 nm84 B_ 0.95 0.03 0.82 0.86 nm85 B_ 0.90 0.06 0.93 0.79 nm86 B_ 0.88 0.05 0.92 0.87 nm87 B_ 0.77 0.02 0.86 0.84 nm15 B_ 0.96 0.15 0.98 0.98 nm89 B_ 0.88 0.06 0.90 0.84 nm90 B_ 0.62 0.05 0.88 0.88 nm91 B_ 0.88 0.06 0.89 0.86 nm92 B_ 0.88 0.04 0.89 0.86 nm93 B_ 0.86 0.06 0.89 0.85 nm94 CD4 + CD4 + CD8 + Th Th Cyto- Marker- CD4 + Central Effect. toxic ID Th2 Mem. Mem. T-Cells B_ 0.86 0.88 0.87 0.87 nm45 B_ 0.85 0.83 0.84 0.88 nm46 B_ 0.89 0.89 0.90 0.92 nm47 B_ 0.93 0.94 0.94 0.93 nm48 B_ 0.96 0.97 0.96 0.95 nm49 B_ 0.89 0.87 0.86 0.89 nm50 B_ 0.84 0.87 0.87 0.92 nm51 B_ 0.94 0.91 0.93 0.94 nm52 B_ 0.90 0.91 0.89 0.89 nm53 B_ 0.95 0.97 0.96 0.96 nm54 B_ 0.90 0.89 0.91 0.92 nm55 B_ 0.87 0.84 0.85 0.87 nm56 B_ 0.91 0.89 0.91 0.89 nm57 B_ 0.88 0.89 0.88 0.88 nm58 B_ 0.88 0.88 0.87 0.87 nm59 B_ 0.91 0.91 0.92 0.91 nm60 B_ 0.87 0.89 0.89 0.90 nm61 B_ 0.90 0.91 0.90 0.90 nm62 B_ 0.98 0.99 0.99 0.99 nm63 B_ 0.88 0.92 0.91 0.91 nm64 B_ 0.87 0.86 0.88 0.88 nm65 B_ 0.87 0.88 0.88 0.89 nm66 B_ 0.90 0.90 0.90 0.92 nm67 B_ 0.98 0.97 0.98 0.98 nm68 B_ 0.87 0.87 0.87 0.89 nm69 B_ 0.88 0.89 0.87 0.90 nm70 B_ 0.86 0.88 0.86 0.90 nm71 B_ 0.88 0.90 0.90 0.90 nm72 B_ 0.96 0.96 0.97 0.96 nm73 B_ 0.91 0.92 0.92 0.92 nm74 B_ 0.86 0.89 0.88 0.89 nm75 B_ 0.90 0.90 0.89 0.88 nm76 B_ 0.91 0.92 0.91 0.92 nm77 B_ 0.94 0.97 0.96 0.97 nm78 B_ 0.92 0.95 0.94 0.95 nm79 B_ 0.97 0.97 0.97 0.97 nm80 B_ 0.95 0.95 0.93 0.93 nm81 B_ 0.80 0.82 0.82 0.91 nm82 B_ 0.92 0.90 0.91 0.90 nm83 B_ 0.94 0.93 0.93 0.93 nm84 B_ 0.83 0.85 0.79 0.96 nm85 B_ 0.83 0.85 0.80 0.85 nm86 B_ 0.89 0.89 0.88 0.93 nm87 B_ 0.85 0.88 0.87 0.88 nm15 B_ 0.98 0.98 0.98 0.80 nm89 B_ 0.81 0.84 0.84 0.90 nm90 B_ 0.88 0.87 0.89 0.88 nm91 B_ 0;82 0.83 0.84 0.89 nm92 B_ 0.88 0.87 0.89 0.90 nm93 B_ 0.86 0.88 0.88 0.84 nm94 Marker- ID NK T-Cells Discovery Fragment B_ 0.86 AGTCATTGTGACTGAAGA nm45 TCAGGCCCACCCAGGCAT TGAGCTCCTCGGGCG B_ 0.85 CGGCCAGGCCCTCATCCA nm46 CCAGAGTAGACCCCAGCA CGAGCAGGCGTCGC B_ 0.91 GCTTTCCACGGCTGTGCGC nm47 CTCGGGGCTGGAGCGGCC CCAAGTGAAGACG B_ 0.92 CGCGGCCCAGGGTTCCGC nm48 CTGGCTGGCACCACCCCTG GAAGGGCAGCCCC B_ 0.88 CAACGTGAAGAAAACGTG nm49 AAATTCTGTCGCTTGTTGC AGCTGACAGCACG B_ 0.87 AAACAGGATCTCTGCAGA nm50 TGGAGCTCAGTGTTATGTG TTTTGGATGCTCG B_ 0.88 CGCCCTGGCCTGAAGGGA nm51 AGAGTCTACAAGGTTTAT AACCCAGAACCGCA B_ 0.93 CGTCCGCCTCGTCCACTCC nm52 TGGCATTTGGGATAAACA TCCTGTCTCAGAC B_ 0.89 CCCTGAAATCGACCCTAA nm53 CAATAATAGAGGTTTGGA TTTGCATGAACACG B_ 0.95 CGCCATCGAGAGACGCAA nm54 CATGGCCCTGGTGACCCTC CTGGTGGAGAACG B_ 0.90 TTGTGAGTCTGGAGGGTTC nm55 CTGGAGAATGGGGCCTGA GGCGTGACCACCG B_ 0.84 CAGGCTACTATTCCTGATG nm56 GAGACCCCCATTTCCGTGG CGGCCCCTGACG B_ 0.91 TCCTGAAAGTCCCTGGCAC nm57 AGGACACCACTACGGGGC TCAGCTGGGTGCG B_ 0.88 CGCAACCAGTATCGCTGC nm58 AGCAACGGGAACTGTATC AACAGCATTTGGTG B_ 0.84 CGGGCCAGCCAGGCCATG nm59 GCATCTGCCTGCTGGGGG CTGTTTTACTGCTG B_ 0.92 TCCTTCAGTGGATTTCTCC nm60 CTGCTGCTGTCACTGAGCT CCACGCTGCTCG B_ 0.88 TTTTTACAAATTGAAAGTT nm61 TACCGCAGCCCAGCTTGA GCCAAGTCTAACG B_ 0.89 CTTTATCCAGCAAGAAGC nm62 CAGCTGTGTGGCAAGCAA TGGAGGTAAGAACG B_ 0.98 CCCCGTGGGACGTGGGGC nm63 AGGCAGCGAGCTTGAGTG TTTGCGCTTCCTCG B_ 0.89 CGGAAAGCCCCATTCACA nm64 GGATTTGCATTGATTTGCC CTGATCTAGTTTG B_ 0.86 CGGGGCAGTTTTGTGGCCT nm65 TTTGCTATTGAATCTGCCA GATGTGTCCAAG B_ 0.84 AGAGCAAGTCAGGCACAC nm66 CATACTCTACCTGGAACA GCTGCTAAACTCCG B_ 0.89 CCCTGACAAAACAAACTC nm67 TGTAAGCTGTGTCAGCCAT GCAAGGCACCACG B_ 0.98 CGCCTTCCGTATCAAAACC nm68 TAAATAGAAGTTGTTGTTA CCGTGTGCCAAT B_ 0.85 CCCACTCTGTGACGCTCAG nm69 AAGATAGCATCCCCTCCTA AGGAACTTGCCG B_ 0.85 CGTCATTGCCAACTCCAAT nm70 GCCTCAATGCACATGGCG GGGCCCAGCCACA B_ 0.90 CTCCCTGAGGACCAGTTTT nm71 TTCCCCTGGGGAGTCATCA TGAATCACTTCG B_ 0.89 CGGCTGCCCAACCCTGACT nm72 CCAGGCTGGACACTGGAG ATGATGCAGACCA B_ 0.96 ACTCAGTGACTGACGTTTA nm73 CGGTCACACGAAGGAATC ACTACACCAAGCG B_ 0.91 CGCACGGGCTCTGCCGTTC nm74 AGAACACAGCCACATCCC GTGATCTCATTTG B_ 0.88 CTGAGTTTTCATCAAACAC nm75 CTGCTGAGCAGCTGGCAC GTGCCAGGACACG B_ 0.86 CTAGAGACAAGCGATGAG nm76 CTGCACTGAGGATCAAGG ATCAGGCATTAGCG B_ 0.78 CATCTGGGTGCTCTGGAAA nm77 CCCAAGAACGGTGCCTAG CTCGGCTCTGTCCG B_ 0.95 GGGCTCGTTCTGGCCTGCG nm78 CTGCGAGGGCTGTGGGCA CTGATGGGCAACG B_ 0.93 CGAGGTCGGTCTCCCACG nm79 ACTGCCCACCATCTGGCCG GCCACCCTGAAAG B_ 0.96 CGTGCCTGCCCCGCCGTGC nm80 ACACACCTCAGCCCCCGG GAGACGTGCCTGC B_ 0.83 CGCCCCCACTCAGTCACAC nm81 GACACTGCTCTCCTGGCCC ACTGCGGCATCC B_ 0.87 CGCTAACATTATGCTCTGT nm82 GGCAGGTTGCCCTGTCTGC TGTGCTCACCTT B_ 0.89 CGCTGGTFGACTGGCAGA nm83 GCAACTTCTGGACCCAGC AGAGTTCAGCTTTG B_ 0.92 CGTGCTCCAAGAAGTACA nm84 AAGAAAAAGTCAAAGCTA CAGCCGCTGACGGC B_ 0.94 CGATATAAAATGAACGCG nm85 CGTTCAAGATTTCCTTCAA CTCATTGTTAGCG B_ 0.76 CGGTTTACCACACCACCCT nm86 TGACTGGGAAATGGGGCT AAGATTTTAATAA B_ 0.86 GGCCAGGGGAGCAGTGAG nm87 TCACTCAGGGCGGGATGG GTGAGGGGCGTCCG B_ 0.84 CGGTCTCTACTCCAAGGG nm15 GCTCACATTCTTGTGCAGA AAACAGAAATGAA B_ 0.98 CGGAGCAGCTGCCGCGCC nm89 TCGAAGTCACTGAAGCAG ACCACACACCTGTG B_ 0.81 ACCCACAGAGAAGCTGCC nm90 ATCTAAATAGGGCTGATTT CGAGTTTTGGACG B_ 0.87 AGCTCCTAGGTTTGAAAA nm91 GTTCTATGTGCGCTTGACC GGGGGGCCTTACG B_ 0.82 CGTTAGCAAACACATAGT nm92 AGCAGAAACACCTGTCAG AGGACAGTGTCTCA B_ 0.86 CGGGATGGAGTTCCCATA nm93 CCGTAGTTCAGAGGCATA GGGACTTCTGCATT B_ 0.79 GACCCCAGGCTGCCATCTT nm94 GGCGCTAACTTCTTCCGAG GCAGAGCCAACG

TABLE 4C CD8 positive T-Cell Markers Baso- phil Marker- Target- Acces- Granu- ID ID SYMBOL sion locytes CD8_nm12 cg CD8A NM_ 0.91 00219921 1145873 CD8_nm13 cg CD8A NM_ 0.87 25939861 00145873 CD8_nm14 cg CD8A NM_ 0.89 18857618 172213 CD8_nm15 cg CD8A NM_ 0.71 03318654 001145873 CD8_nm16 cg PHRF1 NM_ 0.86 25535316 020901 CD8_nm17 cg SBF1 NM_ 0.88 07016730 002972 CD8_nm18 cg CD8A NM_ 0.74 21648425 001145873 TEMRA_ cg — — 0.92 nm1 04467549 TEMRA_ cg PDGFA NM_ 0.89 nm2 20063728 002607 TEMRA_ cg PCID2 NM- 0.98 nm3 06567722 001127203 TEMRA_ cg KIF3C NM_ 0.92 nm4 25002426 002254 TEMRA_ cg C6orf10 NM_ 0.92 nm5 21241195 006781 TEMRA_ cg — — 0.90 nm7 02051545 TEMRA_ cg — — 0.74 nm8 20960322 TEMRA_ cg SOX5 NM_ 0.87 nm9 06147361 152989 TEMRA_ cg TDRD9 NM_ 0.91 nm10 05173889 153046 TEMRA_ cg MYBPH NM_ 0.91 nm11 12080492 004997 TEMRA_ cg SEMA3A NM_ 0.84 nm12 00922200 006080 TEMRA_ cg DEFB114 NM_ 0.74 nm13 19592003 001037499 TEMRA_ cg EHD1 NM_ 0.92 nm14 14317884 006795 TEMRA_ cg C14orf NM_ 0.89 nm15 00879541 166 016039 TEMRA_ cg MSC NM_ 0.90 nm16 24142603 005098 TEMRA_ cg — — 0.89 nm17 05585475 TEMRA_ cg SHANK2 NM_ 0.91 nm18 18080819 012309 TEMRA_ cg NINL NM_ 0.92 nm19 13486641 035176 TEMRA_ cg SGMS1 NM_ 0.87 nm20 13382516 147156 TEMRA_ cg — — 0.87 nm21 26215982 TEMRA_ cg HMCN1 NM_ 0.90 nm22 03221073 031935 TEMRA_ cg CTR9 NM_ 0.93 nm23 02261543 014633 TEMRA_ cg NCRNA NR_ 0.88 nm24 03938110 027021 TEMRA_ cg — — 0.84 nm25 15449516 TEMRA_ cg — — 0.88 nm26 14365420 TEMRA_ cg — — 0.90 nm27 03668556 TEMRA_ cg — — 0.90 nm28 00472528 TEMRA_ cg ANKRD55 NM_ 0.82 nm29 05633605 024669 TEMRA_ cg C6orf10 NM_ 0.90 nm30 27064867 006781 TEMRA_ cg — — 0.88 nm31 18449136 TEMRA_ cg AFF3 NM_ 0.81 nm32 13361307 001025108 TEMRA_ cg LRRK1 NM_ 0.95 nm33 25663823 024652 TEMRA_ cg PLEKHA7 NM_ 0.81 nm34 24722886 175058 TEMRA_ cg — — 0.88 nm35 01252713 TEMRA_ cg — — 0.90 nm36 09851620 TEMRA_ cg AHNAK NM_ 0.86 nm37 26484813 024060 TEMRA_ cg — — 0.85 nm38 25370412 TEMRA_ cg GALR1 NM_ 0.87 nm39 12522833 001480 TEMRA_ cg — — 0.89 nm40 26512948 TEMRA_ cg FSTL4 NM_ 0.85 nm41 06627009 015082 TEMRA_ cg ANK3 NM_ 0.86 nm42 01186212 020987 TEMRA_ cg SYNPO NM_ 0.89 nm43 20940398 001166208 TEMRA_ cg MUC21 NM_ 0.85 nm44 04230397 001010909 TEMRA_ cg — — 0.84 nm45 15617591 TEMRA_ cg — — 0.85 nm46 22112587 TEMRA_ cg LRP5 NM_ 0.88 nm47 15302350 002335 TEMRA_ cg — — 0.89 nm48 19675599 TEMRA_ cg APP NM_ 0.88 nm49 25314245 201413 TEMRA_ cg — — 0.83 nm50 17037931 TEMRA_ cg SERPIN12 NM_ 0.90 nm51 11375831 006217 TEMRA_ cg LPCAT1 NM_ 0.90 nm52 18766691 024830 TEMRA_ cg — — 0.84 nm53 10104542 TEMRA_ cg — — 0.88 nm54 01071903 TEMRA_ cg — — 0.93 nm55 12695059 TEMRA_ cg — — 0.89 nm56 11268546 TEMRA_ cg — — 0.90 nm57 19277516 TEMRA_ cg MED13L NM_ 0.83 nm58 25180759 015335 TEMRA_ cg — — 0.88 nm59 16966340 TEMRA_ cg — — 0.83 nm60 23645373 TEMRA_ cg — — 0.91 nm61 23642827 TEMRA_ cg PPAP2B NM_ 0.88 nm62 27398401 003713.4 TEMRA_ cg OR8S1 NM_ 0.88 nm63 26372842 001005203 TEMRA_ cg — — 0.85 nm64 02936931 TEMRA_ cg CACHD1 NM_ 0.90 nm65 10381153 020925 TEMRA_ cg COL4A2 NM_ 0.88 nm66 06951647 001846 TEMRA_ cg EPS8 NM_ 0.85 nm67 13177421 004447 Eosino- Neutro- Clas- Non- phil phil sical Clas- Marker- Granu- Granu- Mono- sical ID locytes locytes cytes Monocytes CD8_nm12 0.90 0.92 0.90 0.89 CD8_nm13 0.87 0.89 0.56 0.61 CD8_nm14 0.88 0.86 0.90 0.87 CD8_nm15 0.73 0.72 0.73 0.71 CD8_nm16 0.84 0.84 0.83 0.82 CD8_nm17 0.84 0.87 0.77 0.79 CD8_nm18 0.74 0.75 0.55 0.51 TEMRA_ 0.94 0.94 0.65 0.67 nm1 TEMRA_ 0.89 0.89 0.85 0.86 nm2 TEMRA_ 0.98 0.98 0.84 0.85 nm3 TEMRA_ 0.92 0.89 0.87 0.87 nm4 TEMRA_ 0.90 0.91 0.88 0.86 nm5 TEMRA_ 0.91 0.92 0.86 0.85 nm7 TEMRA_ 0.86 0.84 0.61 0.74 nm8 TEMRA_ 0.87 0.88 0.84 0.85 nm9 TEMRA_ 0.88 0.90 0.86 0.82 nm10 TEMRA_ 0.90 0.94 0.87 0.88 nm11 TEMRA_ 0.84 0.88 0.87 0.87 nm12 TEMRA_ 0.87 0.84 0.83 0.82 nm13 TEMRA_ 0.82 0.85 0.82 0.79 nm14 TEMRA_ 0.90 0.89 0.87 0.86 nm15 TEMRA_ 0.95 0.95 0.91 0.88 nm16 TEMRA_ 0.86 0.89 0.83 0.82 nm17 TEMRA_ 0.88 0.90 0.87 0.86 nm18 TEMRA_ 0.93 0.96 0.94 0.94 nm19 TEMRA_ 0.86 0.89 0.79 0.78 nm20 TEMRA_ 0.91 0.90 0.83 0.82 nm21 TEMRA_ 0.88 0.89 0.87 0.85 nm22 TEMRA_ 0.93 0.94 0.88 0.90 nm23 TEMRA_ 0.89 0.87 0.87 0.84 nm24 TEMRA_ 0.86 0.88 0.77 0.79 nm25 TEMRA_ 0.92 0.91 0.90 0.88 nm26 TEMRA_ 0.91 0.92 0.87 0.89 nm27 TEMRA_ 0.89 0.94 0.87 0.81 nm28 TEMRA_ 0.79 0.81 0.81 0.79 nm29 TEMRA_ 0.91 0.91 0.89 0.86 nm30 TEMRA_ 0.90 0.89 0.84 0.83 nm31 TEMRA_ 0.80 0.79 0.78 0.78 nm32 TEMRA_ 0.95 0.95 0.90 0.90 nm33 TEMRA_ 0.81 0.84 0.75 0.72 nm34 TEMRA_ 0.90 0.87 0.87 0.87 nm35 TEMRA_ 0.91 0.92 0.88 0.87 nm36 TEMRA_ 0.89 0.91 0.86 0.85 nm37 TEMRA_ 0.86 0.84 0.85 0.82 nm38 TEMRA_ 0.92 0.92 0.92 0.88 nm39 TEMRA_ 0.91 0.92 0.89 0.83 nm40 TEMRA_ 0.89 0.92 0.89 0.86 nm41 TEMRA_ 0.85 0.82 0.81 0.83 nm42 TEMRA_ 0.87 0.88 0.80 0.78 nm43 TEMRA_ 0.84 0.86 0.82 0.81 nm44 TEMRA_ 0.91 0.89 0.86 0.84 nm45 TEMRA_ 0.87 0.90 0.83 0.82 nm46 TEMRA_ 0.88 0.89 0.85 0.86 nm47 TEMRA_ 0.90 0.86 0.86 0.88 nm48 TEMRA_ 0.88 0.93 0.88 0.86 nm49 TEMRA_ 0.84 0.84 0.85 0.83 nm50 TEMRA_ 0.88 0.88 0.87 0.86 nm51 TEMRA_ 0.91 0.92 0.85 0.86 nm52 TEMRA_ 0.82 0.90 0.83 0.80 nm53 TEMRA_ 0.89 0.90 0.85 0.85 nm54 TEMRA_ 0.91 0.91 0.85 0.86 nm55 TEMRA_ 0.88 0.88 0.86 0.85 nm56 TEMRA_ 0.89 0.87 0.89 0.89 nm57 TEMRA_ 0.91 0.92 0.83 0.83 nm58 TEMRA_ 0.85 0.89 0.86 0.87 nm59 TEMRA_ 0.89 0.89 0.73 0.74 nm60 TEMRA_ 0.92 0.90 0.82 0.83 nm61 TEMRA_ 0.90 0.90 0.86 0.84 nm62 TEMRA_ 0.88 0.90 0.86 0.87 nm63 TEMRA_ 0.84 0.80 0.78 0.80 nm64 TEMRA_ 0.90 0.92 0.88 0.91 nm65 TEMRA_ 0.87 0.86 0.89 0.85 nm66 TEMRA_ 0.80 0.84 0.87 0.79 nm67 Marker- NK NK B- ID classical bright Cells MDSC CD8_nm12 0.90 0.90 0.92 0.85 CD8_nm13 0.84 0.86 0.84 0.81 CD8_nm14 0.88 0.89 0.84 0.85 CD8_nm15 0.74 0.74 0.72 0.70 CD8_nm16 0.86 0.88 0.76 0.83 CD8_nm17 0.88 0.87 0.70 0.82 CD8_nm18 0.57 0.72 0.71 0.58 TEMRA_ 0.84 0.93 0.93 0.89 nm1 TEMRA_ 0.87 0.90 0.89 0.86 nm2 TEMRA_ 0.96 0.98 0.98 0.97 nm3 TEMRA_ 0.91 0.90 0.83 0.87 nm4 TEMRA_ 0.90 0.92 0.73 0.86 nm5 TEMRA_ 0.89 0.92 0.90 0.89 nm7 TEMRA_ 0.78 0.80 0.89 0.82 nm8 TEMRA_ 0.89 0.92 0.63 0.87 nm9 TEMRA_ 0.88 0.93 0.81 0.88 nm10 TEMRA_ 0.93 0.95 0.94 0.91 nm11 TEMRA_ 0.83 0.84 0.74 0.86 nm12 TEMRA_ 0.76 0.79 0.90 0.87 nm13 TEMRA_ 0.91 0.91 0.89 0.84 nm14 TEMRA_ 0.88 0.84 0.84 0.87 nm15 TEMRA_ 0.93 0.95 0.93 0.90 nm16 TEMRA_ 0.89 0.90 0.81 0.88 nm17 TEMRA_ 0.90 0.89 0.82 0.87 nm18 TEMRA_ 0.93 0.95 0.87 0.93 nm19 TEMRA_ 0.86 0.89 0.75 0.84 nm20 TEMRA_ 0.90 0.91 0.81 0.87 nm21 TEMRA_ 0.88 0.90 0.71 0.83 nm22 TEMRA_ 0.91 0.91 0.87 0.91 nm23 TEMRA_ 0.87 0.86 0.75 0.85 nm24 TEMRA_ 0.88 0.85 0.64 0.86 nm25 TEMRA_ 0.89 0.90 0.80 0.88 nm26 TEMRA_ 0.87 0.88 0.85 0.89 nm27 TEMRA_ 0.90 0.93 0.81 0.86 nm28 TEMRA_ 0.80 0.82 0.67 0.79 nm29 TEMRA_ 0.90 0.89 0.82 0.88 nm30 TEMRA_ 0.87 0.86 0.83 0.86 nm31 TEMRA_ 0.81 0.82 0.82 0.80 nm32 TEMRA_ 0.94 0.96 0.95 0.93 nm33 TEMRA_ 0.84 0.85 0.81 0.81 nm34 TEMRA_ 0.88 0.88 0.77 0.85 nm35 TEMRA_ 0.89 0.91 0.84 0.89 nm36 TEMRA_ 0.89 0.86 0.88 0.84 nm37 TEMRA_ 0.83 0.84 0.78 0.85 nm38 TEMRA_ 0.87 0.90 0.89 0.89 nm39 TEMRA_ 0.87 0.89 0.75 0.86 nm40 TEMRA_ 0.91 0.93 0.77 0.87 nm41 TEMRA_ 0.82 0.83 0.91 0.82 nm42 TEMRA_ 0.83 0.83 0.81 0.81 nm43 TEMRA_ 0.84 0.85 0.72 0.83 nm44 TEMRA_ 0.83 0.83 0.79 0.86 nm45 TEMRA_ 0.90 0.89 0.80 0.86 nm46 TEMRA_ 0.89 0.89 0.68 0.84 nm47 TEMRA_ 0.90 0.90 0.79 0.89 nm48 TEMRA_ 0.90 0.91 0.88 0.90 nm49 TEMRA_ 0.85 0.83 0.71 0.81 nm50 TEMRA_ 0.88 0.88 0.77 0.87 nm51 TEMRA_ 0.89 0.90 0.64 0.87 nm52 TEMRA_ 0.84 0.84 0.68 0.81 nm53 TEMRA_ 0.84 0.88 0.79 0.87 nm54 TEMRA_ 0.91 0.92 0.92 0.89 nm55 TEMRA_ 0.88 0.87 0.75 0.85 nm56 TEMRA_ 0.88 0.85 0.82 0.85 nm57 TEMRA_ 0.89 0.90 0.84 0.89 nm58 TEMRA_ 0.87 0.81 0.79 0.87 nm59 TEMRA_ 0.84 0.85 0.83 0.83 nm60 TEMRA_ 0.86 0.90 0.80 0.88 nm61 TEMRA_ 0.90 0.90 0.89 0.88 nm62 TEMRA_ 0.85 0.89 0.79 0.86 nm63 TEMRA_ 0.87 0.87 0.69 0.84 nm64 TEMRA_ 0.89 0.92 0.79 0.90 nm65 TEMRA_ 0.88 0.87 0.82 0.86 nm66 TEMRA_ 0.81 0.87 0.79 0.83 nm67 Marker- CD4 + Th CD4 + CD4 + CD4 + ID naive act. Th1 Th2 CD8_nm12 0.84 0.80 0.80 0.80 CD8_nm13 0.80 0.79 0.79 0.79 CD8_nm14 0.86 0.76 0.78 0.77 CD8_nm15 0.72 0.69 0.70 0.69 CD8_nm16 0.73 0.59 0.67 0.65 CD8_nm17 0.75 0.56 0.58 0.53 CD8_nm18 0.69 0.57 0.70 0.71 TEMRA_ 0.93 0.90 0.83 0.87 nm1 TEMRA_ 0.92 0.80 0.69 0.85 nm2 TEMRA_ 0.96 0.95 0.95 0.97 nm3 TEMRA_ 0.93 0.86 0.59 0.75 nm4 TEMRA_ 0.80 0.92 0.92 0.92 nm5 TEMRA_ 0.91 0.81 0.72 0.75 nm7 TEMRA_ 0.70 0.87 0.85 0.89 nm8 TEMRA_ 0.92 0.75 0.72 0.76 nm9 TEMRA_ 0.88 0.70 0.58 0.62 nm10 TEMRA_ 0.94 0.79 0.64 0.71 nm11 TEMRA_ 0.90 0.74 0.65 0.67 nm12 TEMRA_ 0.71 0.73 0.86 0.83 nm13 TEMRA_ 0.93 0.64 0.63 0.64 nm14 TEMRA_ 0.90 0.79 0.72 0.80 nm15 TEMRA_ 0.95 0.83 0.87 0.83 nm16 TEMRA_ 0.90 0.86 0.81 0.83 nm17 TEMRA_ 0.89 0.68 0.60 0.64 nm18 TEMRA_ 0.96 0.88 0.78 0.79 nm19 TEMRA_ 0.89 0.68 0.67 0.74 nm20 TEMRA_ 0.94 0.77 0.59 0.70 nm21 TEMRA_ 0.92 0.74 0.66 0.76 nm22 TEMRA_ 0.93 0.89 0.89 0.82 nm23 TEMRA_ 0.90 0.69 0.58 0.62 nm24 TEMRA_ 0.91 0.81 0.67 0.71 nm25 TEMRA_ 0.90 0.70 0.61 0.64 nm26 TEMRA_ 0.90 0.89 0.84 0.88 nm27 TEMRA_ 0.94 0.68 0.64 0.69 nm28 TEMRA_ 0.89 0.70 0.60 0.70 nm29 TEMRA_ 0.92 0.68 0.82 0.82 nm30 TEMRA_ 0.89 0.73 0.59 0.70 nm31 TEMRA_ 0.86 0.78 0.59 0.68 nm32 TEMRA_ 0.94 0.66 0.57 0.62 nm33 TEMRA_ 0.86 0.65 0.55 0.57 nm34 TEMRA_ 0.90 0.65 0.53 0.59 nm35 TEMRA_ 0.92 0.68 0.62 0.67 nm36 TEMRA_ 0.92 0.86 0.70 0.75 nm37 TEMRA_ 0.87 0.68 0.59 0.64 nm38 TEMRA_ 0.90 0.85 0.80 0.85 nm39 TEMRA_ 0.90 0.78 0.63 0.67 nm40 TEMRA_ 0.92 0.76 0.69 0.79 nm41 TEMRA_ 0.89 0.85 0.71 0.71 nm42 TEMRA_ 0.89 0.74 0.65 0.72 nm43 TEMRA_ 0.87 0.70 0.57 0.61 nm44 TEMRA_ 0.91 0.64 0.56 0.60 nm45 TEMRA_ 0.90 0.75 0.65 0.73 nm46 TEMRA_ 0.90 0.72 0.62 0.66 nm47 TEMRA_ 0.90 0.63 0.52 0.59 nm48 TEMRA_ 0.92 0.87 0.80 0.87 nm49 TEMRA_ 0.86 0.62 0.54 0.57 nm50 TEMRA_ 0.88 0.68 0.60 0.64 nm51 TEMRA_ 0.92 0.77 0.67 0.84 nm52 TEMRA_ 0.90 0.67 0.60 0.73 nm53 TEMRA_ 0.87 0.73 0.64 0.70 nm54 TEMRA_ 0.86 0.78 0.79 0.83 nm55 TEMRA_ 0.88 0.64 0.57 0.63 nm56 TEMRA_ 0.90 0.71 0.55 0.66 nm57 TEMRA_ 0.93 0.84 0.79 0.82 nm58 TEMRA_ 0.91 0.71 0.63 0.69 nm59 TEMRA_ 0.86 0.72 0.63 0.63 nm60 TEMRA_ 0.89 0.78 0.60 0.79 nm61 TEMRA_ 0.90 0.67 0.57 0.59 nm62 TEMRA_ 0.86 0.78 0.58 0.66 nm63 TEMRA_ 0.92 0.65 0.54 0.62 nm64 TEMRA_ 0.92 0.77 0.63 0.71 nm65 TEMRA_ 0.90 0.66 0.57 0.66 nm66 TEMRA_ 0.87 0.86 0.57 0.60 nm67 CD4 + Th CD4 + Th CD4 + Marker- Central Effect. NKT CD4 + ID Mem. Mem. cells TFH CD8_nm12 0.85 0.85 0.76 0.81 CD8_nm13 0.84 0.82 0.69 0.82 CD8_nm14 0.82 0.79 0.74 0.77 CD8_nm15 0.71 0.72 0.75 0.71 CD8_nm16 0.64 0.68 0.59 0.61 CD8_nm17 0.61 0.59 0.58 0.53 CD8_nm18 0.70 0.75 0.56 0.60 TEMRA_ 0.90 0.89 0.79 0.91 nm1 TEMRA_ 0.82 0.79 0.65 0.83 nm2 TEMRA_ 0.97 0.97 0.77 0.94 nm3 TEMRA_ 0.78 0.76 0.53 0.87 nm4 TEMRA_ 0.74 0.55 0.79 0.85 nm5 TEMRA_ 0.76 0.73 0.65 0.83 nm7 TEMRA_ 0.88 0.87 0.67 0.88 nm8 TEMRA_ 0.75 0.74 0.66 0.78 nm9 TEMRA_ 0.71 0.65 0.68 0.72 nm10 TEMRA_ 0.79 0.74 0.62 0.78 nm11 TEMRA_ 0.76 0.68 0.61 0.72 nm12 TEMRA_ 0.73 0.57 0.66 0.80 nm13 TEMRA_ 0.73 0.72 0.60 0.64 nm14 TEMRA_ 0.81 0.77 0.58 0.82 nm15 TEMRA_ 0.86 0.78 0.59 0.86 nm16 TEMRA_ 0.86 0.86 0.70 0.87 nm17 TEMRA_ 0.70 0.66 0.64 0.64 nm18 TEMRA_ 0.85 0.84 0.74 0.87 nm19 TEMRA_ 0.72 0.69 0.58 0.71 nm20 TEMRA_ 0.74 0.67 0.57 0.82 nm21 TEMRA_ 0.73 0.71 0.63 0.79 nm22 TEMRA_ 0.87 0.89 0.81 0.89 nm23 TEMRA_ 0.69 0.62 0.64 0.67 nm24 TEMRA_ 0.72 0.68 0.58 0.85 nm25 TEMRA_ 0.71 0.68 0.66 0.75 nm26 TEMRA_ 0.89 0.83 0.78 0.88 nm27 TEMRA_ 0.76 0.70 0.61 0.68 nm28 TEMRA_ 0.74 0.71 0.59 0.72 nm29 TEMRA_ 0.76 0.73 0.67 0.72 nm30 TEMRA_ 0.72 0.67 0.71 0.74 nm31 TEMRA_ 0.72 0.66 0.61 0.79 nm32 TEMRA_ 0.70 0.63 0.55 0.65 nm33 TEMRA_ 0.55 0.61 0.65 0.71 nm34 TEMRA_ 0.66 0.61 0.57 0.61 nm35 TEMRA_ 0.72 0.66 0.67 0.74 nm36 TEMRA_ 0.79 0.71 0.67 0.87 nm37 TEMRA_ 0.71 0.69 0.67 0.68 nm38 TEMRA_ 0.87 0.84 0.78 0.85 nm39 TEMRA_ 0.67 0.69 0.60 0.81 nm40 TEMRA_ 0.81 0.77 0.76 0.76 nm41 TEMRA_ 0.75 0.62 0.77 0.81 nm42 TEMRA_ 0.73 0.71 0.55 0.76 nm43 TEMRA_ 0.67 0.65 0.60 0.73 nm44 TEMRA_ 0.69 0.62 0.60 0.64 nm45 TEMRA_ 0.79 0.72 0.67 0.77 nm46 TEMRA_ 0.67 0.64 0.56 0.75 nm47 TEMRA_ 0.65 0.63 0.67 0.65 nm48 TEMRA_ 0.88 0.83 0.75 0.89 nm49 TEMRA_ 0.66 0.62 0.67 0.64 nm50 TEMRA_ 0.70 0.65 0.65 0.69 nm51 TEMRA_ 0.70 0.67 0.67 0.83 nm52 TEMRA_ 0.75 0.73 0.70 0.70 nm53 TEMRA_ 0.73 0.69 0.67 0.73 nm54 TEMRA_ 0.85 0.84 0.72 0.79 nm55 TEMRA_ 0.67 0.63 0.59 0.65 nm56 TEMRA_ 0.76 0.66 0.66 0.72 nm57 TEMRA_ 0.84 0.79 0.63 0.85 nm58 TEMRA_ 0.74 0.71 0.64 0.72 nm59 TEMRA_ 0.72 0.65 0.67 0.70 nm60 TEMRA_ 0.77 0.74 0.61 0.82 nm61 TEMRA_ 0.67 0.64 0.62 0.66 nm62 TEMRA_ 0.71 0.71 0.64 0.73 nm63 TEMRA_ 0.69 0.61 0.54 0.64 nm64 TEMRA_ 0.74 0.69 0.67 0.78 nm65 TEMRA_ 0.72 0.66 0.63 0.66 nm66 TEMRA_ 0.71 0.60 0.56 0.65 nm67 CD8 + Cyto- CD8 + CD8 + Th Marker- to- toxic naive CD8 + Central ID T-Cells T8n_1 act. Mem. CD8_nm12 0.08 0.10 0.18 0.29 CD8_nm13 0.01 0.07 0.15 0.11 CD8_nm14 0.20 0.22 0.30 0.47 CD8_nm15 0.15 0.17 0.22 0.20 CD8_nm16 0.21 0.13 0.45 0.45 CD8_nm17 0.19 0.21 0.26 0.39 CD8_nm18 0.22 0.25 0.31 0.27 TEMRA_ 0.58 0.86 0.29 0.28 nm1 TEMRA_ 0.93 0.85 0.38 0.35 nm2 TEMRA_ 0.89 0.97 0.93 0.76 nm3 TEMRA_ 0.65 0.92 0.56 0.46 nm4 TEMRA_ 0.92 0.92 0.91 0.87 nm5 TEMRA_ 0.71 0.91 0.46 0.55 nm7 TEMRA_ 0.72 0.89 0.86 0.83 nm8 TEMRA_ 0.65 0.89 0.44 0.40 nm9 TEMRA_ 0.72 0.89 0.49 0.59 nm10 TEMRA_ 0.76 0.92 0.60 0.69 nm11 TEMRA_ 0.72 0.86 0.50 0.47 nm12 TEMRA_ 0.82 0.86 0.73 0.72 nm13 TEMRA_ 0.68 0.89 0.49 0.49 nm14 TEMRA_ 0.70 0.89 0.49 0.42 nm15 TEMRA_ 0.69 0.91 0.36 0.41 nm16 TEMRA_ 0.67 0.85 0.39 0.41 nm17 TEMRA_ 0.74 0.88 0.47 0.66 nm18 TEMRA_ 0.84 0.95 0.56 0.75 nm19 TEMRA_ 0.61 0.86 0.39 0.34 nm20 TEMRA_ 0.59 0.93 0.32 0.36 nm21 TEMRA_ 0.66 0.79 0.58 0.59 nm22 TEMRA_ 0.82 0.92 0.71 0.73 nm23 TEMRA_ 0.69 0.86 0.39 0.47 nm24 TEMRA_ 0.67 0.89 0.62 0.50 nm25 TEMRA_ 0.73 0.89 0.51 0.63 nm26 TEMRA_ 0.81 0.88 0.80 0.81 nm27 TEMRA_ 0.73 0.89 0.42 0.55 nm28 TEMRA_ 0.71 0.85 0.39 0.57 nm29 TEMRA_ 0.80 0.92 0.57 0.57 nm30 TEMRA_ 0.74 0.88 0.45 0.55 nm31 TEMRA_ 0.65 0.84 0.58 0.53 nm32 TEMRA_ 0.76 0.93 0.49 0.49 nm33 TEMRA_ 0.59 0.82 0.34 0.35 nm34 TEMRA_ 0.69 0.89 0.43 0.58 nm35 TEMRA_ 0.74 0.92 0.50 0.66 nm36 TEMRA_ 0.75 0.90 0.63 0.73 nm37 TEMRA_ 0.74 0.83 0.54 0.55 nm38 TEMRA_ 0.87 0.86 0.80 0.83 nm39 TEMRA_ 0.69 0.91 0.50 0.41 nm40 TEMRA_ 0.77 0.89 0.50 0.64 nm41 TEMRA_ 0.79 0.86 0.67 0.44 nm42 TEMRA_ 0.70 0.83 0.46 0.52 nm43 TEMRA_ 0.66 0.86 0.42 0.52 nm44 TEMRA_ 0.72 0.87 0.48 0.50 nm45 TEMRA_ 0.64 0.89 0.39 0.46 nm46 TEMRA_ 0.65 0.90 0.51 0.52 nm47 TEMRA_ 0.71 0.92 0.41 0.56 nm48 TEMRA_ 0.80 0.90 0.59 0.72 nm49 TEMRA_ 0.71 0.83 0.43 0.55 nm50 TEMRA_ 0.74 0.89 0.53 0.68 nm51 TEMRA_ 0.62 0.86 0.45 0.39 nm52 TEMRA_ 0.71 0.88 0.38 0.52 nm53 TEMRA_ 0.74 0.87 0.57 0.65 nm54 TEMRA_ 0.65 0.88 0.39 0.54 nm55 TEMRA_ 0.71 0.87 0.46 0.59 nm56 TEMRA_ 0.76 0.89 0.69 0.72 nm57 TEMRA_ 0.74 0.89 0.54 0.49 nm58 TEMRA_ 0.70 0.86 0.54 0.69 nm59 TEMRA_ 0.69 0.83 0.50 0.63 nm60 TEMRA_ 0.59 0.87 0.34 0.37 nm61 TEMRA_ 0.72 0.88 0.44 0.65 nm62 TEMRA_ 0.75 0.87 0.60 0.67 nm63 TEMRA_ 0.61 0.91 0.35 0.35 nm64 TEMRA_ 0.75 0.93 0.49 0.60 nm65 TEMRA_ 0.76 0.87 0.47 0.51 nm66 TEMRA_ 0.67 0.83 0.45 0.45 nm67 Marker- CD8 + Th CD8 + ID Effect. Mem. TEMRA NK T cells CD8_nm12 0.13 0.07 0.23 CD8_nm13 0.07 0.05 0.10 CD8_nm14 0.39 0.14 0.35 CD8_nm15 0.21 0.17 0.25 CD8_nm16 0.44 0.29 0.47 CD8_nm17 0.26 0.24 0.29 CD8_nm18 0.28 0.24 0.27 TEMRA_ 0.19 0.12 0.19 nm1 TEMRA_ 0.28 0.11 0.15 nm2 TEMRA_ 0.59 0.22 0.42 nm3 TEMRA_ 0.40 0.12 0.27 nm4 TEMRA_ 0.89 0.14 0.87 nm5 TEMRA_ 0.38 0.14 0.27 nm7 TEMRA_ 0.66 0.11 0.74 nm8 TEMRA_ 0.40 0.12 0.25 nm9 TEMRA_ 0.50 0.11 0.47 nm10 TEMRA_ 0.55 0.16 0.45 nm11 TEMRA_ 0.51 0.11 0.41 nm12 TEMRA_ 0.61 0.12 0.79 nm13 TEMRA_ 0.38 0.11 0.25 nm14 TEMRA_ 0.36 0.16 0.34 nm15 TEMRA_ 0.43 0.20 0.30 nm16 TEMRA_ 0.35 0.19 0.27 nm17 TEMRA_ 0.56 0.13 0.51 nm18 TEMRA_ 0.58 0.23 0.56 nm19 TEMRA_ 0.29 0.13 0.22 nm20 TEMRA_ 0.19 0.16 0.19 nm21 TEMRA_ 0.45 0.15 0.34 nm22 TEMRA_ 0.80 0.24 0.63 nm23 TEMRA_ 0.40 0.13 0.38 nm24 TEMRA_ 0.35 0.15 0.18 nm25 TEMRA_ 0.52 0.16 0.48 nm26 TEMRA_ 0.74 0.22 0.54 nm27 TEMRA_ 0.38 0.16 0.32 nm28 TEMRA_ 0.47 0.11 0.29 nm29 TEMRA_ 0.48 0.18 0.56 nm30 TEMRA_ 0.48 0.15 0.35 nm31 TEMRA_ 0.51 0.12 0.39 nm32 TEMRA_ 0.40 0.18 0.35 nm33 TEMRA_ 0.40 0.10 0.25 nm34 TEMRA_ 0.49 0.12 0.44 nm35 TEMRA_ 0.57 0.17 0.54 nm36 TEMRA_ 0.53 0.19 0.40 nm37 TEMRA_ 0.56 0.13 0.58 nm38 TEMRA_ 0.81 0.23 0.79 nm39 TEMRA_ 0.46 0.16 0.30 nm40 TEMRA_ 0.64 0.19 0.57 nm41 TEMRA_ 0.57 0.16 0.49 nm42 TEMRA_ 0.43 0.14 0.33 nm43 TEMRA_ 0.43 0.13 0.26 nm44 TEMRA_ 0.41 0.13 0.40 nm45 TEMRA_ 0.42 0.17 0.31 nm46 TEMRA_ 0.45 0.15 0.46 nm47 TEMRA_ 0.49 0.15 0.45 nm48 TEMRA_ 0.61 0.24 0.51 nm49 TEMRA_ 0.45 0.11 0.47 nm50 TEMRA_ 0.49 0.16 0.50 nm51 TEMRA_ 0.43 0.19 0.34 nm52 TEMRA_ 0.56 0.14 0.50 nm53 TEMRA_ 0.54 0.17 0.59 nm54 TEMRA_ 0.44 0.22 0.30 nm55 TEMRA_ 0.43 0.14 0.42 nm56 TEMRA_ 0.53 0.17 0.44 nm57 TEMRA_ 0.44 0.22 0.31 nm58 TEMRA_ 0.55 0.17 0.41 nm59 TEMRA_ 0.47 0.14 0.40 nm60 TEMRA_ 0.37 0.19 0.24 nm61 TEMRA_ 0.47 0.16 0.35 nm62 TEMRA_ 0.59 0.17 0.45 nm63 TEMRA_ 0.36 0.13 0.20 nm64 TEMRA_ 0.50 0.20 0.48 nm65 TEMRA_ 0.49 0.16 0.44 nm66 TEMRA_ 0.40 0.13 0.36 nm67 Marker- ID NK T-Cells Discovery Fragment CD8_nm12 0.18 TAAAATCTACAGTAC ACCACAAGGGTCAC AATACTGTTGTGCGC ACATCG CD8_nm13 0.12 CGGAAATCAGCTTGG GGGCCTTCTAGCCCT GCAGCTCAGAAAAG TGTCAG CD8_nm14 0.39 CGAGGTGGATATTAG CAACTCCTTTAGCAG GGCTCAATGGCGTCT TAGAA CD8_nm15 0.24 TCCAACCAATTGTGC TCTCCCAATTCCAAC AACCAAATGAAGCTT CAACG CD8_nm16 0.50 ATTTTTTACTTTCTAT GTGAAATTCATCATC AAATGAGGATGTGCA CTCG CD8_nm17 0.30 GCCCACCGGGGTTGC CCTGGTGTTGCCCCC ATCTGTAGAGAAGTT AGGCG CD8_nm18 0.27 CGCTGTTTTGCTCAG GCTGGCCTTGGGACT CCTGAGCTCCAGTGA TCCTC TEMRA_ 0.33 TCTGTCAGAGGGCTG nm1 TTGTGGGATTATAAG AGCCCACTTGTGAAA TTGCG TEMRA_ 0.13 GTCTTTGCCTGACAC nm2 CTTCTGTGAGGTTTG CGGGCTTCATTTTAA ATCCG TEMRA_ 0.60 CGAGGCGCTGGCGA nm3 AGCACGAGGCCTTCT TCATTCGCTGCGAA TCTTCC TEMRA_ 0.36 CGAAAGCAAGCGAG nm4 TGAATTAGGATTTCA AAGTGCCCTAATAGT GTGAGT TEMRA_ 0.85 CGGCACAGATAAAA nm5 ATACAGAGACAATG GTTCCGACCCAGAGA TGAGGCT TEMRA_ 0.27 GTCCGCAGTAATAAC nm7 AACCAAAGACACAT ATTCTCAGGCAATGA TAACCG TEMRA_ 0.57 CATGAGAAAACTTCT nm8 TTAAGACCACCTGTA GAATTCTGCAATCAC ATACG TEMRA_ 0.23 CGGAAGAATGAAAA nm9 GCTAATATTATTGTG TGGCATGATGACTGT CTCTTC TEMRA_ 0.38 CGCCCCACCCCAGAA nm10 CCAGCTAGCACCCAA GGGCTAGGCAGCCTG CTACT TEMRA_ 0.42 TGCTGTGGGCCTCAG nm11 TTTTCCACCTGTTAC AGAGAACCCCTCGCC CTTCG TEMRA_ 0.35 CGGGAATCTGTCTGT nm12 GTTACAAAGCAACTA GACTCACCCTATTGG CCTAA TEMRA_ 0.76 CGGTCGTTGTAAAAG nm13 AGACTGTCTTGAGAG TGAAAAGCAAATAG ACATAT TEMRA_ 0.27 CCTTCTCTTCCCCCC nm14 AGGCTATGACTTTGC AGCCGTCCTGGAGTG GTTCG TEMRA_ 0.17 GGGGTTATATATTTT nm15 TGACCAAATTCACCA TTACTCATTTGGCAT TTTCG TEMRA_ 0.40 CGCGCAGGGTGGGC nm16 GGCTTACCATAGCAA GTGATCCTGCGATAG GGAACG TEMRA_ 0.27 CGGTAGACAAATGAT nm17 AGACATTTGTTGAAT CAAGCTGTGAGTTGG AGATC TEMRA_ 0.52 CGCCACCCCACCTTC nm18 ATCCACGGACTCCAG GTACTGTAGGGCTGG GAAAG TEMRA_ 0.49 CAGTGACGTGGTGGG nm19 GAGCGTGTGCTTGTG TAGGGACAGCTTTCC AGGCG TEMRA_ 0.20 CGTGCCCAGCTTTTC nm20 TATGGGAAAAATTGT TCTTCAGACAGAGCA TGAAT TEMRA_ 0.15 GCGTACACACCCTGA nm21 TAAGGTGTCAAGAAC CTCCGTTTGAGTACC CCTCG TEMRA_ 0.30 ACTTAGAGCCCACCA nm22 TGAAGCATCTTTTCT GTTGCTTACACTGACT CACCG TEMRA_ 0.60 GGCCTTCTCTTTCTG nm23 GATGGCTGGTCACTG TCTGAGTCCTGATCT GACCG TEMRA_ 0.34 CGGTATTTCAGTTAC nm24 ACTCTGTTGATTCAA AAGAAGGTTGTTTGT CCAAG TEMRA_ 0.22 TTGCTCCAGCACTAC nm25 AGAGCAGATTTGGA GCAGTCAGGTGGGG AAGCTCG TEMRA_ 0.44 CGGTCCTCACCTCAC nm26 TAGATCACCATGACT CACTGGGTAGATGGG CTATT TEMRA_ 0.50 CGCTATTGCTAAGTA nm27 AAACCCATGTGTTTT CAGTCATGGTTAGCA GCAGG TEMRA_ 0.32 CGAGGACGAATCTTG nm28 AGGCCTCCACTGGTC TACACGGACAGAAG CACGCC TEMRA_ 0.32 CGTGGGAAAGTAAT nm29 ACAGGGAGGGAACA GCAGCCCATAAAAA GAACGTTA TEMRA_ 0.49 CTCATCTTAAGGATG nm30 CTTATTATCATAATG CTTTTTATTAATTCCTA ATCG TEMRA_ 0.38 CTCTTAACCTGGTGG nm31 TCTTTCACTAGCTTT ACAAAGGTGATACA GTTTCG TEMRA_ 0.33 CGAGGCTCTGCACAG nm32 GTAAACTCAAGGGTT ACCCTGTGCTTTGAA ACCTT TEMRA_ 0.38 TCAGCCCCGGAGGGC nm33 AGGCGCCAGTCCATC AGCTTGTATGTCTGT CCTCG TEMRA_ 0.26 CGAGTGTGGAGCTAT nm34 GATTGGAACCTAGTT CAGGCTCCAAAGCCA CACTC TEMRA_ 0.39 CGACCATTCTCACAA nm35 GACATTGAACAGAG AATAAGAGGAGAGA AAAAGGC TEMRA_ 0.46 AAGTTCCCAA=TTAGAT nm36 GACTCACTTCAGGAG GGCCAGGAACCATTCT GTTCG TEMRA_ 0.28 CGGCTCTGCCAGGAC nm37 CCACCAGCCAATTCC AAGTCGAGCAAAAG AATCCA TEMRA_ 0.49 ACTGTTGATCCTGGG nm38 AGTCTCTGGCCTTGT ATTTATGACTTATCA ATTCG TEMRA_ 0.75 ATTCTGTCTAGTCTTT nm39 GGTCCCATAGAAATT ATTATCTACATCAAC CTCG TEMRA_ 0.33 ACACTTCTGGCAAAT nm40 AGTTCATCTAATTAG AACCATGGGAAACC CCTCCG TEMRA_ 0.56 CGGGGATTCCAACCC nm41 CAGGGCACCTCTCTG GCATTCCCATTAAGG AAGCC TEMRA_ 0.51 ATTTGTAACATCACA nm42 AGAGTTAGAAGACC CCATATTGCTTGAGC TTTTCG TEMRA_ 0.35 CGAGGCTTGTGTCTCT nm43 TGGCCACCACTGTCT TCTGGAATTATAGGA GTAAA TEMRA_ 0.33 CGAGTAAAATGATG nm44 ATCCTCACTCTATGG AAGAGAAGCAGAGC TGGCCCC TEMRA_ 0.35 CGCCTGGAATTTCTT nm45 GAAACACCCTTATAC ATGCATAAAACTGTA GGTGG TEMRA_ 0.31 CGGTCTTGGGTGGCC nm46 CATAGGAGATTAAG AATTTCCTATTATCC AAGCTG TEMRA_ 0.38 CGGCCAGGCTGCAAT nm47 GCACATGGCCGCCCT CATTGGCAGGGTCAC ATGAG TEMRA_ 0.40 CGCCACAAATGAGTA nm48 AAGCAGGTCTAGCA GGCTTGTCGTTGAG TTACTG TEMRA_ 0.55 CGAGACACCTGGGG nm49 ATGAGAATGAACAT GCCCATTTCCAGAAA GCCAAAG TEMRA_ 0.42 CCCCTTTTTCCCAGG nm50 GACCCACAGAACTGT GAGCAAGAAATAAA TGTTCG TEMRA_ 0.48 CGGTCTCTGCCATTG nm51 GTAGGAAAAGTAAT GGACTATTTCTGGAT AAATCA TEMRA_ 0.34 CGGAATAAAACCACT nm52 GAAACACAATCAGG GCTACGTGCATTACC TGTGGC TEMRA_ 0.45 CGGATGCCTATCTGT nm53 TCCTGACCCCCAAGG TCCCTCAGGATCTGC TGGGA TEMRA_ 0.52 CGCAAATCCAAACCA nm54 TATCAGGGTTTCACA GCTAGAGAGAAGGA GTCAAT TEMRA_ 0.43 GGTGATTACAGCAGA nm55 TGACCCCATCTGCCT GGTGCCTGACTTTAT TTTCG TEMRA_ 0.42 GGGGTTGACCATGGC nm56 TGGTAACAGGGGACT CTGGTTGGCCAGTGG CATCG TEMRA_ 0.43 CGAGTTTAACCCCAC nm57 TTGGAGCCAGAAAG ATGGGCCAAATCAAC ACCAAG TEMRA_ 0.34 CACAGACTAATGATA nm58 ATCTTTGGGAAATTT GGGTCTACCATAAAT ACTCG TEMRA_ 0.51 AGGTTAAAACCAAG nm59 GGCTCAGACTACAGG TGTGTGTAGCATGTG TACACG TEMRA_ 0.41 TTCACTGCAGATGAA nm60 ATGGGCTTCTCATGC TACCTCAGTTACCAG AATCG TEMRA_ 0.26 CGCATACTTTCAGGG nm61 AGAGGCACTATTCTT GGCTTTAAGTTCATG AGTAA TEMRA_ 0.40 CGACAATTTCAATCC nm62 AGAGTGTTAAGTGCT GTTACAGAGGAGCTG GGGAG TEMRA_ 0.45 CGTAGTCTGACACAG nm63 GAGTCCACTTAGCCA TTGATCTGTGTGGCT CAATT TEMRA_ 0.21 GACTGAAACTTGCAC nm64 CAGTTCTGAATGCCT CTAACCTTGGTTGTA TAACG TEMRA_ 0.40 CGAGGCTGAATGAA nm65 ATCCAATTGGAACTC ACTTGAACACTGTTT TGATGT TEMRA_ 0.40 GTGTCCCAGGAAAG nm66 GCCCACTAGTGGGTC CCGGTGTGGGACCCA CCCCCG TEMRA_ 0.37 ACAGTGAGCTATGCC nm67 CTGAATGACAGACAC CATATTCACAGGCAA AATCG

TABLE 4D Follicular helper T cells-marker Baso- Eosino- phil phil Marker- Target- Granu- Granu- ID ID SYMBOL Accession locytes locytes TFH_ cg130 PRKCZ NM_00 0.91 0.90 nm1 77150 2744 TFH_ cg112 PRKCZ NM_00 0.86 0.82 nm2 27141 2744 TFH_ cg270 MKL2 NM_01 0.85 0.87 nm3 64482 4048 TFH_ cg213 GIMAP8 NM_17 0.92 0.91 nm4 77860 5571 TFH_ cg157 LIF NM_00 0.88 0.89 nm5 22603 2309 TFH_ cg001 NFATC1 NM_00 0.90 0.91 nm6 51768 6162 TFH_ cg152 NFATC1 NM_00 0.94 0.95 nm7 60951 6162 TFH_ cg164 C2orf48 NM_18 0.97 0.96 nm8 21411 2626 TFH_ cg263 ATXN1 NM_00 0.97 0.95 nm9 93261 0332 TFH_ cg108 DNAJC5 NM_02 0.97 0.98 nm10 42070 5219 TFH_ cg092 MAF NM_17 0.92 0.91 nm11 32021 5571 TFH_ cg131 SPATS2L NM_01 0.96 0.97 nm12 44059 5535 TFH_ cg261 TMCC1 NM_00 0.90 0.90 nm13 75815 1017395 TFH_ cg071 SERINC5 NM_17 0.91 0.78 nm14 72701 8276 TFH_ cg219 CD28 NM_00 0.88 0.86 nm15 11000 6139 TFH_ cg152 LPP NM_00 0.92 0.92 nm16 13399 5578 TFH_ cg035 ABTB1 NM_17 0.95 0.94 nm17 96635 2028 TFH_ cg104 ZHX1 NM_00 0.91 0.91 nm18 51262 7222 TFH_ cg013 — — 0.90 0.89 nm19 49034 TFH_ cg158 PTPN2 NM_08 0.85 0.86 nm20 73449 0423 THH_ cg161 — — 0.85 0.89 nm21 52136 TFH_ cg209 LIPC NM_00 0.90 0.92 nm22 68717 0236 TFH_ cg250 CXCR5 NM_00 0.90 0.92 nm23 87423 1716 TFH_ cg080 CTSB NM_14 0.88 0.92 nm24 12294 7780 TFH_ cg174 NUB1 NM_01 0.92 0.91 nm25 10313 6118 TFH_ cg043 SLC25A12 NM_00 0.89 0.91 nm26 37734 3705 TFH_ cg150  HIPK2 NM_02 0.97 0.97 nm27 39797 2740 TFH_ cg275 — — 0.96 0.95 nm28 86885 TFH_ cg207  RNF216 NM_20 0.91 0.86 nm29 02205 7111 TFH_ cg068 FAM6A NM_02 0.87 0.88 nm30 46719 1238 TFH_ cg238 CLEC7A NM_02 0.87 0.88 nm31 92568 2570 TFH_ cg240 — — 0.90 0.90 nm32 33742 TFH_ cg032 ST7 NM_01 0.82 0.88 nm33 80299 8412 TFH_ cg163 IL6ST NM_17 0.89 0.86 nm34 75820 5767 TFH_ cg113 ZNF589 NM_01 0.88 0.90 nm35 07417 6089 TFH_ cg137 DLEU1 — 0.90 0.92 nm36 74342 TFH_ cg216 ANKFY1 NM_01 0.91 0.91 nm37 53149 6376 TFH_ cg146 SMURF2 NM_02 0.87 0.89 nm38 24950 2739 TFH_ cg131 FAM65B — 0.67 0.78 nm39 42152 TFH_ cg158 ATXN7L1 NM_02 0.78 0.80 nm40 73112 0725 TFH_ cg233 PCBP3 — 0.84 0.80 nm41 42358 TFH_ cg225 — — 0.91 0.90 nm42 35163 TFH_ cg136 PRRC2B NM_01 0.92 0.92 nm43 37151 3318 TFH_ cg264 ARHGAP35 NM_00 0.90 0.88 nm44 46535 4491 TFH_ cg063 SOD2 NM_00 0.47 0.63 nm45 46099 0636 TFH_ cg130 SETD3 NM_03 0.93 0.92 nm46 49261 2233 TFH_ cg060 ARID1B NM_01 0.85 0.88 nm47 19273 7519 TFH_ cg007 PVT1 NR_00 0.80 0.78 nm48 80520 3367 TFH_ cg071 — — 0.95 0.96 nm49 67688 TFH_ cg271 IL17A NM_00 0.69 0.89 nm50 668844 2190 TFH_ cg188 CNIH NM_01 0.91 0.92 nm51 834724 4184 TFH_ cg118 — — 0.85 0.90 nm52 87733 TFH_  cg020 — — 0.96 0.96 nm53 03272 TFH_ cg202 PHACTR2 NR_02 0.90 0.92 nm54 98778 7113 TFH_ cg190 ITPKB NM_00 0.74 0.67 mn55 30737 2221 TFH_ cg193 HDAC4 NM_00 0.98 0.97 nm56 24997 6037 Non- Neutro- Clas- clas- phil sical sical NK Marker- Granu- Mono- Mono- clas- NK ID locytes cytes cytes sical bright TFH_ 0.91 0.89 0.89 0.88 0.87 nm1 TFH_ 0.83 0.86 0.85 0.87 0.88 nm2 TFH_ 0.89 0.89 0.88 0.84 0.68 nm3 TFH_ 0.91 0.92 0.91 0.92 0.89 nm4 TFH_ 0.90 0.89 0.90 0.80 0.80 nm5 TFH_ 0.91 0.93 0.87 0.91 0.82 nm6 TFH_ 0.95 0.95 0.95 0.92 0.88 nm7 TFH_ 0.97 0.96 0.97 0.96 0.95 nm8 TFH_ 0.96 0.97 0.97 0.96 0.94 nm9 TFH_ 0.97 0.97 0.97 0.95 0.90 nm10 TFH_ 0.91 0.93 0.92 0.91 0.90 nm11 TFH_ 0.98 0.98 0.98 0.97 0.95 nm12 TFH_ 0.92 0.90 0.88 0.88 0.81 nm13 TFH_ 0.84 0.84 0.87 0.90 0.92 nm14 TFH_ 0.89 0.91 0.89 0.89 0.88 nm15 TFH_ 0.91 0.90 0.87 0.89 0.76 nm16 TFH_ 0.95 0.95 0.95 0.94 0.93 nm17 TFH_ 0.92 0.90 0.91 0.91 0.91 nm18 TFH_ 0.88 0.88 0.86 0.87 0.87 nm19 TFH_ 0.87 0.88 0.85 0.86 0.76 nm20 THH_ 0.90 0.88 0.89 0.88 0.88 nm21 TFH_ 0.92 0.94 0.92  0.91 0.87 nm22 TFH_ 0.92 0.91 0.90 0.86 0.81 nm23 TFH_ 0.92 0.86 0.76 0.91 0.89 nm24 TFH_ 0.92 0.91 0.89 0.92 0.89 nm25 TFH_ 0.87 0.88 0.88 0.86 0.78 nm26 TFH_ 0.98 0.97 0.98 0.25 0.62 nm27 TFH_ 0.96 0.96 0.95 0.94 0.92 nm28 TFH_ 0.91 0.89 0.87 0.91 0.90 nm29 TFH_ 0.90 0.89 0.87 0.87 0.76 nm30 TFH_ 0.88 0.81 0.82 0.86 0.79 nm31 TFH_ 0.90 0.90 0.90 0.90 0.91 nm32 TFH_ 0.89 0.84 0.86 0.87 0.78 nm33 TFH_ 0.88 0.89 0.87 0.88 0.77 nm34 TFH_ 0.90 0.87 0.87 0.89 0.87 nm35 TFH_ 0.90 0.88 0.91 0.89 0.82 nm36 TFH_ 0.91 0.91 0.92 0.88 0.76 nm37 TFH_ 0.90 0.90 0.89 0.87 0.82 nm38 TFH_ 0.86 0.87 0.85 0.85 0.82 nm39 TFH_ 0.84 0.87 0.85 0.86 0.86 nm40 TFH_ 0.76 0.84 0.83 0.86 0.85 nm41 TFH_ 0.90 0.91 0.90 0.89 0.85 nm42 TFH_ 0.93 0.91 0.91 0.90 0.87 nm43 TFH_ 0.90 0.92 0.93 0.91 0.87 nm44 TFH_ 0.79 0.84 0.77 0.78 0.78 nm45 TFH_ 0.93 0.93 0.92 0.90 0.89 nm46 TFH_ 0.91 0.88 0.88 0.84 0.82 nm47 TFH_ 0.80 0.81 0.85 0.82 0.80 nm48 TFH_ 0.95 0.96 0.94 0.95 0.95 nm49 TFH_ 0.92 0.92 0.89 0.87 0.80 nm50 TFH_ 0.91 0.92 0.91 0.89 0.87 nm51 TFH_ 0.90 0.92 0.89 0.88 0.83 nm52 TFH_  0.96 0.97 0.96 0.96 0.94 nm53 TFH_ 0.94 0.92 0.89 0.86 0.79 nm54 TFH_ 0.83 0.81 0.84 0.79 0.82 mn55 TFH_ 0.98 0.98 0.97 0.79 0.94 nm56 CD4 + Marker- B- Th CD4 + CD4 + ID Cells MDSC naive act. Th1 TFH_ 0.86 0.85 0.92 0.33 0.63 nm1 TFH_ 0.83 0.81 0.89 0.28 0.60 nm2 TFH_ 0.80 0.77 0.89 0.17 0.66 nm3 TFH_ 0.92 0.90 0.79 0.38 0.73 nm4 TFH_ 0.88 0.84 0.89 0.24 0.35 nm5 TFH_ 0.81 0.88 0.92 0.37 0.71 nm6 TFH_ 0.82 0.92 0.90 0.14 0.29 nm7 TFH_ 0.96 0.93 0.97 0.44 0.68 nm8 TFH_ 0.97 0.96 0.96 0.33 0.87 nm9 TFH_ 0.50 0.94 0.97 0.29 0.87 nm10 TFH_ 0.91 0.90 0.91 0.25 0.56 nm11 TFH_ 0.90 0.96  0.97 0.42 0.88 nm12 TFH_ 0.78 0.88 0.87 0.25 0.54 nm13 TFH_ 0.88 0.84 0.93 0.25 0.63 nm14 TFH_ 0.91 0.87 0.85 0.15 0.38 nm15 TFH_ 0.90 0.84 0.91 0.36 0.88 nm16 TFH_ 0.92 0.91 0.54 0.29 0.62 nm17 TFH_ 0.87 0.89 0.90 0.22 0.49 nm18 TFH_ 0.93 0.88 0.91 0.36 0.73 nm19 TFH_ 0.57 0.85 0.82 0.18 0.56 nm20 THH_ 0.86 0.87 0.83 0.20 0.40 nm21 TFH_ 0.72 0.89 0.85 0.36 0.63 nm22 TFH_ 0.08 0.85 0.83 0.19 0.59 nm23 TFH_ 0.89 0.80 0.81 0.23 0.46 nm24 TFH_ 0.81 0.89 0.92 0.31 0.66 nm25 TFH_ 0.86 0.86 0.84 0.28 0.74 nm26 TFH_ 0.98 0.91 0.10 0.21 0.52 nm27 TFH_ 0.94 0.89 0.95 0.32 0.81 nm28 TFH_ 0.79 0.89 0.89 0.29 0.80 nm29 TFH_ 0.75 0.83 0.87 0.24 0.58 nm30 TFH_ 0.67 0.81 0.86 0.17 0.38 nm31 TFH_ 0.92 0.89 0.91 0.41 0.72 nm32 TFH_ 0.84 0.85 0.86 0.33 0.62 nm33 TFH_ 0.88 0.80 0.18 0.25 0.69 nm34 TFH_ 0.86 0.85 0.36 0.24 0.57 nm35 TFH_ 0.81 0.88 0.89 0.21 0.45 nm36 TFH_ 0.90 0.86 0.85 0.38 0.70 nm37 TFH_ 0.87 0.85 0.90 0.31 0.61 nm38 TFH_ 0.83 0.81 0.69 0.19 0.42 nm39 TFH_ 0.50 0.81 0.67 0.19 0.48 nm40 TFH_ 0.87 0.83 0.78 0.34 0.71 nm41 TFH_ 0.91 0.89 0.73 0.31 0.65 nm42 TFH_ 0.92 0.88 0.83 0.35 0.76 nm43 TFH_ 0.90 0.89 0.92 0.38 0.65 nm44 TFH_ 0.85 0.77 0.86 0.24 0.45 nm45 TFH_ 0.90 0.87 0.76 0.23 0.48 nm46 TFH_ 0.62 0.87 0.90 0.32 0.54 nm47 TFH_ 0.65 0.77 0.87 0.20 0.42 nm48 TFH_ 0.94 0.93 0.96 0.31 0.53 nm49 TFH_ 0.70 0.86 0.88 0.24 0.72 nm50 TFH_ 0.93 0.89 0.76 0.41 0.76 nm51 TFH_ 0.89 0.83 0.58 0.23 0.40 nm52 TFH_  0.89 0.92 0.96 0.35 0.58 nm53 TFH_ 0.73 0.89 0.92 0.39 0.79 nm54 TFH_ 0.82 0.80 0.41 0.28 0.68 mn55 TFH_ 0.98 0.93 0.73 0.41 #DIV/0! nm56 CD4 + CD4 + Th Th CD4 + Marker- CD4 + Central Effect. NK CD4 + ID Th2 Mem. Mem. T cells TFH TFH_ 0.51 0.55 0.54 0.78 0.23 nm1 TFH_ 0.42 0.58 0.57 0.78 0.18 nm2 TFH_ 0.59 0.62 0.63 0.56 0.08 nm3 TFH_ 0.51 0.72 0.71 0.83 0.28 nm4 TFH_ 0.42 0.47 0.44  0.58 0.13 nm5 TFH_ 0.65 0.80 0.74 0.74 0.23 nm6 TFH_ 0.26 0.38 0.29 0.55 0.10 nm7 TFH_ 0.59 0.69 0.69 0.80 0.32 nm8 TFH_ 0.79 0.87 0.85 0.87 0.16 nm9 TFH_ 0.80 0.86 0.87 0.89 0.16 nm10 TFH_ 0.62 0.53 0.47 0.65 0.10 nm11 TFH_ 0.80 0.91 0.85 0.88 0.24 nm12 TFH_ 0.49 0.60 0.56 0.75 0.12 nm13 TFH_ 0.45 0.57 0.62 0.75 0.12 nm14 TFH_ 0.32 0.41 0.25 0.62 0.09 nm15 TFH_ 0.77 0.85 0.86 0.67 0.15 nm16 TFH_ 0.58 0.57 0.58 0.72 0.15 nm17 TFH_ 0.37 0.55 0.45 0.65 0.12 nm18 TFH_ 0.74 0.76 0.70 0.78 0.16 nm19 TFH_ 0.54 0.52 0.52 0.73 0.11 nm20 THH_ 0.50 0.45 0.42 0.60 0.10 nm21 TFH_ 0.54 0.64 0.62 0.76 0.16 nm22 TFH_ 0.52 0.58 0.58 0.68 0.10 nm23 TFH_ 0.49 0.50 0.45 0.68 0.15 nm24 TFH_ 0.65 0.66 0.65 0.77 0.19 nm25 TFH_ 0.62 0.65 0.61 0.63 0.15 nm26 TFH_ 0.58 0.44 0.45 0.51 0.09 nm27 TFH_ 0.55 0.72 0.69 0.71 0.20 nm28 TFH_ 0.58 0.70 0.78 0.86 0.21 nm29 TFH_ 0.44 0.59 0.59 0.63 0.12 nm30 TFH_ 0.35 0.43 0.29 0.63 0.11 nm31 TFH_ 0.67 0.74 0.77 0.84 0.22 nm32 TFH_ 0.52 0.60 0.61 0.66 0.16 nm33 TFH_ 0.47 0.56 0.66 0.65 0.14 nm34 TFH_ 0.41 0.43 0.54 0.64 0.16 nm35 TFH_ 0.35 0.40 0.39 0.55 0.13 nm36 TFH_ 0.70 0.70 0.70 0.60 0.19 nm37 TFH_ 0.44 0.60 0.52 0.77 0.18 nm38 TFH_ 0.31 0.40 0.33 0.67 0.13 nm39 TFH_ 0.35 0.39 0.41 0.54 0.12 nm40 TFH_ 0.60 0.70 0.72 0.74 0.19 nm41 TFH_ 0.60 0.68 0.53 0.68 0.23 nm42 TFH_ 0.65 0.69 0.73 0.71 0.25 nm43 TFH_ 0.74 0.69 0.63 0.72 0.25 nm44 TFH_ 0.45 0.48 0.44 0.64 0.12 nm45 TFH_ 0.41 0.47 0.42 0.65 0.18 nm46 TFH_ 0.46 0.60 0.60 0.66 0.18 nm47 TFH_ 0.27 0.44 0.37 0.61 0.11 nm48 TFH_ 0.47 0.57 0.50 0.69 0.26 nm49 TFH_ 0.61 0.62 0.60 0.63 0.19 nm50 TFH_ 0.47 0.64 0.71 0.83 0.26 nm51 TFH_ 0.39 0.40 0.44 0.66 0.17 nm52 TFH_  0.50 0.55 0.57 0.66 0.27 nm53 TFH_ 0.62 0.79 0.71 0.68 0.23 nm54 TFH_ 0.48 0.52 0.59 0.63 0.16 mn55 TFH_ #DIV/0! 0.70 0.68 0.72 0.29 nm56 CD8 + CD8 + CD8 + Cytoto- Th Th Marker- toxic CD8 + CD8 + Central  Effect. ID T-Cells naive act. Mem. Mem. TFH_ 0.86 0.86 0.68 0.77 0.82 nm1 TFH_ 0.81 0.85 0.67 0.73 0.74 nm2 TFH_ 0.88 0.82 0.70 0.66 0.76 nm3 TFH_ 0.88 0.88 0.81 0.90 0.88 nm4 TFH_ 0.78 0.89 0.64 0.71 0.62 nm5 TFH_ 0.92 0.85 0.86 0.86 0.90 nm6 TFH_ 0.87 0.91 0.63  0.66 0.73 nm7 TFH_ 0.97 0.95 0.87 0.93 0.95 nm8 TFH_ 0.96 0.94 0.93 0.93 0.94 nm9 TFH_ 0.97 0.95 0.85 0.90 0.93 nm10 TFH_ 0.90 0.91 0.85 0.88 0.62 nm11 TFH_ 0.98 0.96 0.94 0.95 0.97 nm12 TFH_ 0.84 0.84 0.78 0.72 0.81 nm13 TFH_ 0.88 0.90 0.79 0.82 0.87 nm14 TFH_ 0.82 0.87 0.61 0.77  0.60  nm15 TFH_ 0.93 0.90 0.90 0.74 0.84 nm16 TFH_ 0.61 0.50 0.77 0.84 0.84 nm17 TFH_ 0.82 0.90 0.68 0.77 0.77 nm18 TFH_ 0.88 0.91 0.82 0.84 0.82 nm19 TFH_ 0.89 0.86 0.71 0.78 0.76 nm20 THH_ 0.83 0.85 0.70 0.80 0.68 nm21 TFH_ 0.86 0.89 0.73 0.83 0.80 nm22 TFH_ 0.84 0.82 0.54 0.81 0.77 nm23 TFH_ 0.90 0.89 0.85 0.91 0.88 nm24 TFH_ 0.89 0.89 0.84 0.89 0.87 nm25 TFH_ 0.87 0.84 0.84 0.79 0.77 nm26 TFH_ 0.60 0.60 0.87 0.87 0.83 nm27 TFH_ 0.91 0.93 0.74 0.81 0.80 nm28 TFH_ 0.90 0.88 0.85 0.90 0.89 nm29 TFH_ 0.80 0.84 0.69 0.59 0.77 nm30 TFH_ 0.85 0.87 0.79 0.80 0.69 nm31 TFH_ 0.90 0.89 0.79 0.87 0.90 nm32 TFH_ 0.85 0.80 0.82 0.69 0.77 nm33 TFH_ 0.72 0.59 0.81 0.76 0.84 nm34 TFH_ 0.73 0.69 0.77 0.82 0.83 nm35 TFH_ 0.81 0.89 0.61 0.69 0.66 nm36 TFH_ 0.86 0.85 0.78 0.72 0.77 nm37 TFH_ 0.85 0.86 0.76 0.77 0.78 nm38 TFH_ 0.84 0.81 0.65 0.81 0.76 nm39 TFH_ 0.79 0.87 0.73 0.79 0.69 nm40 TFH_ 0.83 0.83 0.78 0.77 0.80 nm41 TFH_ 0.85 0.82 0.84 0.84 0.83 nm42 TFH_ 0.90 0.86 0.83 0.85 0.86 nm43 TFH_ 0.89 0.86 0.81 0.82 0.80 nm44 TFH_ 0.80 0.84 0.77 0.80 0.74 nm45 TFH_ 0.78 0.89 0.61 0.66 0.62 nm46 TFH_ 0.81 0.83 0.74 0.71 0.77 nm47 TFH_ 0.73 0.83 0.56 0.67 0.69 nm48 TFH_ 0.88 0.95 0.71 0.80 0.83 nm49 TFH_ 0.84 0.87 0.76 0.81 0.62 nm50 TFH_ 0.85 0.85 0.85 0.89 0.87 nm51 TFH_ 0.76 0.88 0.58 0.69 0.66 nm52 TFH_  0.90 0.96 0.65 0.62 0.80 nm53 TFH_ 0.86 0.91 0.67 0.74 0.74 nm54 TFH_ 0.69 0.60 0.69 0.63 0.82 mn55 TFH_ 0.91 0.84 0.87 0.81 0.85 nm56 CD8 + Marker- NK NK Discovery  ID TEMRA T cells T-cells Fragment TFH_ 0.86 0.87 0.86 CGTGCTGTGCCC nm1 TCGATGCTCCAG CACCTATGGCCC TGCTGACCCTGG AG TFH_ 0.72 0.75 0.67 CGAGGCACGGCC nm2 ACTTCTCCAAAG GGCCAAGCTTCC CTCGTCAGGCCGG CT TFH_ 0.81 0.78 0.82 AGAGAGCTGACA nm3 AGGGCATGCACG ATTAATTGCACA CTCGCACACCCA CG TFH_ 0.92 0.91 0.93 CGTAAAGTCTGC nm4 TCCAAAGATGGC CTCCAGTTTCGC CACAGCTGTTTT GT TFH_ 0.73 0.65 0.60 CGGGACCAGAA nm5 GATCCTCAACCC CAGTGCCCTCAG CCTCCACAGCAA GCT TFH_ 0.88 0.90 0.90 CGGCTCTTCAGG nm6 TACAGAGATCTG AACTTGGAAAGA CCTGCCTTTCTA AA TFH_ 0.93 0.81 0.85 CGGCTCGCTCAG nm7 CCATCAGGTGCC CCACGACACACA GGTGGTTTGGGG GT TFH_ 0.95 0.94 0.97 CGCCCGTCGTTC nm8 ATGTCGATTCTC TCAGTCAATCAA AACGCTGCCACA GC TFH_ 0.96 0.96 0.96 ATGCAGCGATGT nm9 GGCCGGGAGITA GCATGAAGCGTG GTTATTCTATCA CG TFH_ 0.96 0.94 0.97 CGCTGTCCGCCC nm10 TTCGCCACCCAC CGCGCCTGCTGC TCAGGAATGTTC CA TFH_ 0.91 0.79 0.73 TGTTTCTCTTTAC nm11 CGTTCAATGCAT ATGTGCGCAAGC CACCTCTGATGC G TFH_ 0.98 0.96 0.97 GGCAGAGTCATC nm12 TGCGTGGCGCAC ACTGTTGTATAT GCTGCACGTACA CG TFH_ 0.84 0.87 0.84 GCTTTCTCATTTT nm13 TCCGTTCCTCCA CCCACTGGCTGG TTATGGGGGTTC G TFH_ 0.88 0.77 0.88 CGTACTTGCAAA nm14 GTAATACAGAAA CGTGACTTTCGG CAGCTACCCAAG AT TFH_ 0.87 0.79 0.78 CGGTTAATTATG nm15 GAAAAACAGCTT GTTAAGCAAATG CTAATGTAAGAA GA TFH_ 0.87 0.80 0.94 GTTTTAATAAAG nm16 CACTATCAAAAA GACGGCACAGA GTTTCGGTTGCC ACG TFH_ 0.87 0.88 0.87 AGAGGAATCGTG nm17 GTGCTTTGCAAA TGTGTATCAAGG CCTTTGAATGCA CG TFH_ 0.69 0.72 0.75 AAGAAATCCACT nm18 AATGAGTGTTCA CTAGCACAGGCA CATTTATGTTTTC G TFH_ 0.84 0.84 0.81 ACTGCACATATC nm19 TTTTTGAAAGAC AGCTTTTTAAGG TATGACTCACTA CG TFH_ 0.84 0.86 0.81 CGCCAAGTATTC nm20 AGCATCTCTTTG GAATTCATTTGT CAGCCTCTCTGG TT THH_ 0.80 0.69 0.68 CGTCAAGCTGGC nm21 AGAATTTTAGAG GCATCTCATTTA AATTAGATCTGG CC TFH_ 0.89 0.90 0.89 CGGGTGACTCAT nm22 AGAGAGTGATTA GAAGTAAAAAG GTTCTGGAAATT CCC TFH_ 0.83 0.85 0.81 TGATGAGTTGTG nm23 AGGCAGGTCGCG GCCCTACTGCCT CAGGAGACGATG CG TFH_ 0.89 0.90 0.88 CGCCTAACCAGT nm24 TGGAAACAGGGC TGTCCTGAGCCA ACACCCAGGAGA GC TFH_ 0.87 0.89  0.84 CGGTAGAGTCTA nm25 ATTTGCAAGATG TAAATGCAGAAA ATAGACATTTCA GC TFH_ 0.82 0.81 0.81 CGACGGACACTA nm26 AAACTGGGTCAG AAAACTTGGGTT CTAAACTCCTGT GC TFH_ 0.96 0.87 0.85 CGGTACCATGAT nm27 ACGTGCCGCAGA ATGTTCCTGCTG CGACCGTAAAGA AC TFH_ 0.84 0.77 0.83 CGCCCGCGCCTT nm28 TCCCAGGCTCAA GGCCTCCCTGCC CACCAGGCAGGT GG TFH_ 0.90 0.89 0.90 CACTAGTAACTC nm29 TCCGGTGTCTAG AGTTAGTACTGA TGGACTCCCTGC CG TFH_ 0.69 0.82 0.76 CGCTGAGATTGT nm30 TTGAGTTGTTTTT CTTAATTAGTAT TTCATAGCTAAG T TFH_ 0.83 0.81 0.80 CGGTTAAATTAA nm31 TTAATGTCAGAC TTAGTTGTGAGA GTAATGAAGGCA GC TFH_ 0.89 0.88 0.90 CGCTGGGAGAAC nm32 TTGAGCGGGGAG CCCAGCACCACA CACCCACTTGCC TC TFH_ 0.85 0.81 0.83 CTGCTCTAGGAA nm33 TATATTTACATA CATGTATTTCTC CTATTTCTTCATC G TFH_ 0.84 0.86 0.90 CGGGGAATCCCT nm34 CCCTGCCACTGT AGAGGATTTATG GGTTGCCCTTAA GT TFH_ 0.89 0.86 0.87 GAGTGTATCCTC nm35 TGATGTACACTA AGAGCGGACTTG AGGCTAAAGTTT CG TFH_ 0.60 0.62 0.63 TGGGAGACTTGT nm36 AATTGTGTACCT GTTTGCATTGTTT AGCCTATGCATC G TFH_ 0.84 0.80 0.79 CGGTGCTTGAGG nm37 AAGATGCATCTG CTCTTGACACTG ACATACTCGAAG GA TFH_ 0.76 0.73 0.76 CGGCATCCGAAT nm38 ATTCTAGCCCTG GCAGACCTCTTA GCTGCTTTGTTG AT TFH_ 0.74 0.74 0.79 TCCCAATCAGTG nm39 AGACCTCAAATA ATGAACTTGGCT CTCATTTATACA CG TFH_ 0.73 0.71 0.65 ATTCAAAGACGC nm40 TTGCTCTGAAAG CCCGAAATTCAG TCTTTCTGAAGA CG TFH_ 0.83 0.81 0.80 TACCAGAGTGCC nm41 TGTGCTGTTGTA TCCTGACACACC AGGTACTGCATA CG TFH_ 0.90 0.86 0.81 CGCACAAAAATG nm42 TAGAAAGAATAT TGGAGACGGAA AATTGTGAATGT ACC TFH_ 0.89 0.87 0.90 GGAAATCGAATC nm43 GTGGATTCACCA GGCCGGTGCTGG CACACTCACCCT CG TFH_ 0.84 0.85 0.85 GTTGTCAGAATT nm44 TCCTTCCCTTTAA AGGCTGAATAGG CCAGGCGTGATC G TFH_ 0.76 0.71 0.69 CCACTACAAAAA nm45 CAGTCATAAAGA GCTTAACATACT CAGCATAACGAT CG TFH_ 0.62 0.62 0.62 CGATGGGTAGGT nm46 GGAATAACAGCC CCCTCCCAAAGC TTAGCAACAACA GC TFH_ 0.78 0.78 0.79 AGAATGGAAAAT nm47 GTAAATTAAGCC TTTGTTTTCCATC ATCATTCTCATC GC TFH_ 0.67 0.73 0.76  CGCCACCTCCAT nm48 GCTGTGTTTCTG TGGCTGGAGCTT TTCTGCACTGGA AA TFH_ 0.56 0.88 0.79 TGCCTGAGGCCG nm49 CCCGCTGTTCAG CGGAAGAGCCA ACATCTGTGCTA TCG TFH_ 0.78 0.66 0.63 CGGTCCAGAAAT nm50 ACTATCTGGTCC AAATCAGCAAGA GCATCGCACGTT AG TFH_ 0.89 0.89 0.89  AATTACCCTCAT nm51 GATGAACATTTC CCTACTCTGAGT AAAGATGCTATC CG TFH_ 0.76 0.80 0.75 TAAATAAAGATC nm52 ATCTGGTCCAAG GATGGCAAATAT GTGGCACAAGTA CG TFH_  0.86 0.84 0.89 AAGGCGCAGCCA nm53 AGGACTATTACA CCTCTGGCTGCT CGGACGCATCTT CG TFH_ 0.90 0.76 0.78 CGGGTGGCTGAA nm54 TGGAAAAACAA ATGGGGCTTCAC CTGTGACTCAGA CCA TFH_ 0.85 0.79 0.86 CGGCTCAGGAGA mn55 CTGAAACATCCA AAGCCTGAATTG GTCCTTATATCA TG TFH_ 0.97 0.89 0.92 CGCCCCGCACGT nm56 ACTGTGTGCCTC GTTCTTTATCTGT GTTCGTTTATTC A

TABLE 4E positive T cell Marker Baso- Eosino- phil phil Marker- Target- Granu- Granu- ID ID SYMBOL Accession locytes locytes nCD4_ cg24885 CA6 NM_0012 0.91 0.93 nm1 723 15 nCD4_ cg26280 — — 0.92 0.92 nm2 976 nCD4_ cg00912 — — 0.89 0.90 nm3 164 nCD4_ cg04116 MAN1C1 NM_0203 0.89 0.87 nm4 354 79 nCD4_ cg13484 — — 0.92 0.92 nm5 324 nCD4_ cg10555 MAN1C1 NM_0203 0.88 0.90 nm6 744 79 nCD4_ cg08639 STIM2 NM_0011 0.91 0.92 nm7 389 69117 nCD_ cg25737 — — 0.04 0.03 meth1 313 nCD_ cg13921 ARHGEF2 NM_0047 0.21 0.25 meth1 921 23 nCD_ cg03290 DUSP5 NM_0044 0.10 0.15 meth1 131 19 nCD_ cg04742 ITGAX NM_0008 0.00 0.01 meth1 550 87 nCD_ cg21268 GGA1 NM_0010 0.03 0.03 meth1 578 01560 CD4mem_ cg11106 RAP1GDS1 NM_0011 0.80 0.92 nm1 864 00427 CD4mem_ cg08877 GPR63 NM_0011 0.85 0.85 nm2 853 43957 CD4mem_ cg14108 SDCCAG3 NM_0010 0.95 0.95 nm3 380 39708 CD4mem_ cg10328 SS18L1 NM_1989 0.92 0.92 nm4 548 35 CD4mem_ cg03188 TALDO1 NM_0067 0.82 0.71 nm5 793 55 CD4mem_ cg09187 — — 0.91 0.91 nm6 865 CD4mem_ cg04936 FAM38A NM_0011 0.78 0.82 nm7 610 42864 CD4mem_ cg21685 PON2 NM_0003 0.84 0.86 nm8 655 05 CD4mem_ cg2l132 ALLC NM_0184 0.96 0.96 nm9 587 36 CD4mem_ cg04026 HLA- NM_0021 0.78 0.76 nm10 937 DRB1 24 CD4mem_ cg18591 — — 0.91 0.91 nm11 489 CD4mem_ cg26296 FARS2 NM_0065 0.75 0.82 nm12 371 67 CD4mem_ cg26899 HCFC1 NM_0053 0.89 0.89 nm13 005 34 CD4mem_ cg08299 — — 0.93 0.94 nm14 859 CD4mem_ cg05450 NUBP1 NM_0024 0.73 0.70 nm15 979 84 CD4mem_ cg15700 HLA- NR_00129 0.79 0.88 nm16 429 DRB6 8 CD4mem_ cg25232 OSBPL5 NM_0011 0.79 0.74 nm17 888 44063 CD4mem_ cg05606 — — 0.86 0.89 nm18 115 CD4mem_ cg15654 HLA- NR_00129 0.87 0.86 nm19 485 DRB6 8 CD4mem_ cg20601 ERICH1 NM_2073 0.88 0.88 nm20 736 32 CD4mem_ cg01419 PLAT NM_0009 0.87 0.91 nm2l 713 30 CD4mem_ cg13213 KIAA12 NM_0207 0.95 0.95 nm22 216 10 21 CD4mem_ cg23812 FLG2 NM_0010 0.92 0.91 nm23 489 14342 CD4mem_ cg08916 GNRHR NM_0004 0.91 0.88 nm24 385 06 CD4mem_ cg13011 PAGE2M NM_0010 0.87 0.89 nm25 976 15038 CD4mem_ cg09354 — — 0.94 0.95 nm26 553 CD4mem_ cg00944 TRRAP NM_0034 0.86 0.83 nm27 599 96 CD4mem_ cg07904 — — 0.96 0.98 nm28 290 CD4mem_ cg22626 SMYD3 NM_0011 0.91 0.91 nm29 897 67740 CD4mem_ cg18887 SMURF1 NM_0204 0.89 0.89 nm30 230 29 CD4mem_ cg16490 — — 0.79 0.63 nm31 805 CD4mem_ cg18203 — — 0.71 0.73 nm32 203 CD4mem_ cg22951 AHRR NM_0207 0.82 0.83 nm33 524 31 CD4mem_ cg07712 TBCD NM_0059 0.90 0.90 nm34 165 93 CD4mem_ cg01201 — — 0.82 0.82 nm35 914 CD4mem_ cg07951 — — 0.82 0.85 nm36 602 CD4mem_ cg21498 — — 0.86 0.89 nm37 326 CD4mem_ cg11791 RANBP3L NM_1450 0.82 0.70 nm38 078 00 CD4mem_ cg15613 MCC NM_0023 0.76 0.80 nm39 905 87 CD4mem_ cg09307 — — 0.87 0.86 nm40 431 CD4mem_ cg21911 CD28 NM_0061 0.88 0.86 nm41 000 39 CD4mem_ cg20770 ILA- NM_0021 0.87 0.87 nm42 572 DQB1 23 CD4mem_ cg22787 — — 0.62 0.65 nm43 186 Neutro- Non- phil Classical classical CD4 + Marker- Granu- Mono- Mono- Th CD4 + ID locytes cytes cytes naive Th1 nCD4_ 0.90 0.92 0.91 0.18 0.85 nm1 nCD4_ 0.94 0.93 0.92 0.21 0.87 nm2 nCD4_ 0.90 0.89 0.91 0.19 0.81 nm3 nCD4_ 0.88 0.88 0.88 0.16 0.74 nm4 nCD4_ 0.87 0.91 0.92 0.22 0.88 nm5 nCD4_ 0.93 0.91 0.92 0.20 0.81 nm6 nCD4_ 0.92 0.93 0.92 0.19 0.69 nm7 nCD_ 0.03 0.03 0.03 0.61 0.14 meth1 nCD_ 0.05 0.03 0.05 0.69 0.16 meth1 nCD_ 0.08 0.02 0.03 0.63 0.07 meth1 nCD_ 0.01 0.01 0.01 0.69 0.14 meth1 nCD_ 0.04 0.03 0.02 0.74 0.24 meth1 CD4mem_ 0.88 0.89 0.89 0.92 0.90 nm1 CD4mem_ 0.89 0.88 0.90 0.93 0.87 nm2 CD4mem_ 0.94 0.96 0.96 0.92 0.11 nm3 CD4mem_ 0.91 0.93 0.92 0.94 0.90 nm4 CD4mem_ 0.84 0.87 0.86 0.73 0.91 nm5 CD4mem_ 0.82 0.80 0.80 0.87 0.93 nm6 CD4mem_ 0.83 0.84 0.86 0.88 0.85 nm7 CD4mem_ 0.87 0.85 0.85 0.83 0.75 nm8 CD4mem_ 0.97 0.97 0.96 0.97 0.97 nm9 CD4mem_ 0.74 0.76 0.72 0.88 0.75 nm10 CD4mem_ 0.91 0.90 0.89 0.69 0.18 nm11 CD4mem_ 0.76 0.80 0.75 0.79 0.55 nm12 CD4mem_ 0.91 0.90 0.93 0.73 0.56 nm13 CD4mem_ 0.93 0.94 0.93 0.93 0.94 nm14 CD4mem_ 0.78 0.77 0.68 0.83 0.82 nm15 CD4mem_ 0.89 0.88 0.85 0.74 0.76 nm16 CD4mem_ 0.90 0.92 0.92 0.97 0.94 nm17 CD4mem_ 0.91 0.92 0.92 0.90 0.88 nm18 CD4mem_ 0.89 0.90 0.90 0.89 0.87 nm19 CD4mem_ 0.88 0.90 0.87 0.87 0.83 nm20 CD4mem_ 0.91 0.90 0.89 0.81 0.14 nm2l CD4mem_ 0.97 0.97 0.96 0.96 0.96 nm22 CD4mem_ 0.92 0.90 0.91 0.92 0.91 nm23 CD4mem_ 0.90 0.89 0.87 0.92 0.53 nm24 CD4mem_ 0.87 0.89 0.88 0.83 0.37 nm25 CD4mem_ 0.93 0.94 0.92 0.91 0.90 nm26 CD4mem_ 0.88 0.87 0.82 0.72 0.15 nm27 CD4mem_ 0.97 0.97 0.97 0.97 0.97 nm28 CD4mem_ 0.91 0.90 0.91 0.88 0.89 nm29 CD4mem_ 0.89 0.89 0.87 0.71 0.24 nm30 CD4mem_ 0.71 0.73 0.71 0.73 0.70 nm31 CD4mem_ 0.74 0.70 0.71 0.76 0.52 nm32 CD4mem_ 0.84 0.84 0.84 0.83 0.74 nm33 CD4mem_ 0.91 0.91 0.91 0.91 0.91 nm34 CD4mem_ 0.83 0.82 0.82 0.87 0.46 nm35 CD4mem_ 0.82 0.84 0.83 0.88 0.78 nm36 CD4mem_ 0.87 0.89 0.83 0.88 0.14 nm37 CD4mem_ 0.74 0.75 0.76 0.61 0.66 nm38 CD4mem_ 0.81 0.82 0.82 0.84 0.44 nm39 CD4mem_ 0.86 0.86 0.87 0.81 0.19 nm40 CD4mem_ 0.89 0.91 0.89 0.85 0.38 nm41 CD4mem_ 0.88 0.87 0.86 0.88 0.83 nm42 CD4mem_ 0.84 0.80 0.81 0.84 0.85 nm43 CD4 + CD4 + CD8 + Th Th Cyto- Marker- CD4 + Central Efftect. toxic NK ID Th2 Mem. Mem. T-Cells T-Cells nCD4_ 0.89 0.82 0.90 0.54 0.92 nm1 nCD4_ 0.83 0.77 0.88 0.68 0.92 nm2 nCD4_ 0.72 0.75 0.87 0.52 0.91 nm3 nCD4_ 0.57 0.59 0.75 0.57 0.89 nm4 nCD4_ 0.78 0.66 0.74 0.66 0.92 nm5 nCD4_ 0.68 0.65 0.81 0.54 0.93 nm6 nCD4_ 0.62 0.59 0.69 0.55 0.87 nm7 nCD_ 0.14 0.24 0.15 0.35 0.07 meth1 nCD_ 0.35 0.34 0.29 0.43 0.05 meth1 nCD_ 0.19 0.25 0.16 0.42 0.05 meth1 nCD_ 0.16 0.27 0.17 0.11 0.01 meth1 nCD_ 0.23 0.32 0.25 0.17 0.04 meth1 CD4mem_ 0.91 0.47 0.02 0.89 0.85 nm1 CD4mem_ 0.87 0.44 0.03 0.91 0.83 nm2 CD4mem_ 0.08 0.26 0.13 0.67 0.59 nm3 CD4mem_ 0.90 0.48 0.11 0.93 0.93 nm4 CD4mem_ 0.91 0.46 0.03 0.91 0.88 nm5 CD4mem_ 0.92 0.50 0.12 0.94 0.90 nm6 CD4mem_ 0.85 0.44 0.06 0.86 0.80 nm7 CD4mem_ 0.73 0.46 0.04 0.86 0.87 nm8 CD4mem_ 0.98 0.55 0.31 0.97 0.98 nm9 CD4mem_ 0.75 0.46 0.06 0.84 0.76 nm10 CD4mem_ 0.09 0.27 0.15 0.70 0.57 nm11 CD4mem_ 0.53 0.45 0.04 0.70 0.72 nm12 CD4mem_ 0.57 0.20 0.17 0.76 0.71 nm13 CD4mem_ 0.94 0.59 0.14 0.93 0.93 nm14 CD4mem_ 0.81 0.48 0.03 0.82 0.69 nm15 CD4mem_ 0.80 0.39 0.13 0.72 0.72 nm16 CD4mem_ 0.94 0.52 0.19 0.95 0.86 nm17 CD4mem_ 0.85 0.49 0.16 0.86 0.80 nm18 CD4mem_ 0.88 0.44 0.18 0.87 0.90 nm19 CD4mem_ 0.82 0.43 0.17 0.87 0.83 nm20 CD4mem_ 0.16 0.22 0.19 0.72 0.68 nm2l CD4mem_ 0.96 0.59 0.26 0.96 0.95 nm22 CD4mem_ 0.91 0.51 0.19 0.92 0.90 mn23 CD4mem_ 0.51 0.18 0.27 0.88 0.83 nm24 CD4mem_ 0.30 0.25 0.19 0.77 0.69 nm25 CD4mem_ 0.93 0.61 0.20 0.93 0.70 nm26 CD4mem_ 0.20 0.24 0.16 0.81 0.66 nm27 CD4mem_ 0.96 0.20 0.46 0.95 0.93 nm28 CD4mem_ 0.87 0.54 0.23 0.90 0.89 nm29 CD4mem_ 0.15 0.26 0.21 0.71 0.68 nm30 CD4mem_ 0.69 0.28 0.05 0.86 0.83 nm31 CD4mem_ 0.56 0.21 0.04 0.77 0.67 nm32 CD4mem_ 0.75 0.43 0.16 0.80 0.71 nm33 CD4mem_ 0.91 0.22 0.44 0.91 0.90 nm34 CD4mem_ 0.87 0.42 0.16 0.84 0.82 nm35 CD4mem_ 0.79 0.20 0.17 0.80 0.70 nm36 CD4mem_ 0.18 0.35 0.24 0.74 0.59 nm37 CD4mem_ 0.60 0.07 0.09 0.65 0.71 nm38 CD4mem_ 0.44 0.10 0.33 0.74 0.61 nm39 CD4mem_ 0.24 0.33 0.26 0.66 0.53 nm40 CD4mem_ 0.32 0.41 0.25 0.82 0.78 nm41 CD4mem_ 0.83 0.27 0.42 0.83 0.79 nm42 CD4mem_ 0.83 0.27 0.25 0.80 0.82 nm43 Marker- ID Discovery Fragment nCD4_ CGGATAGATTAGTTC nm1 TGGAATAATGCCTGA GACACAGCACCCAG AACCTC nCD4_ TGTTGTGGGAAGCTT nm2 TCCCGTGCGCTGTAG GATGTTTAGCAGCAC CCTCG nCD4_ GTACTCTTACACTCA nm3 CGGGGGTGCCGGGC CCCTGGAACCTGCAA CTCACG nCD4_ CGGAATTTTTTAGTG nm4 CAAAATATTTACTAG TGTGAGGCAGAACAT TATTA nCD4_ CGAGTCTATGTAATT nm5 AAGAGACTGAGAAT TACACTAGGGACCTC CTATAG nCD4_ GTAGCTAAGTAAGG nm6 GGCATTCATTTCTCC CTTTCTTGTTAAGGA ACTACG nCD4_ CATACTTCAAACATA nm7 ACGTGTCTTAAAACA ACTTTTGATCTCTGT CACCG nCD_ CGCCCCCGCGGGGCC meth1 CAGCCAGATGTCAGC TGCAGTTATTAGCCT GGGCG nCD_ CGTGTCTTGATTCCA meth1 CCTTTAGAGGCTGCC CAGGGTTTCACACCC GACCC nCD_ CGAGCCTGTGGCTTT meth1 CAAGCTGTGGACATC TGGCCTAGCTAGATT TCTAC nCD_ CGCAACTGATCCGAG meth1 GACAGGCTCGGCCTC CCACACGCCCCCACC CCCCA nCD_ GTCTCCTTCATTCATT meth1 GGCCTCTGCTGGGGC CTCCTATGGGTGTCT TACG CD4mem_ CCATACCACTTGTGC nm1 ATGCATGTGATGTTC TAATACCAATTGAAG AACCG CD4mem_ GGCAGTGTTGACTGC nm2 GTTCCATACCGGGAC ATCCAACACAACATT TGTCG CD4mem_ CGGATGCCCTCGTGG nm3 GCCAGCTATCCCCAG GCACAGCGAGACAG CGACGT CD4mem_ CCACCGTGCCCAGCT nm4 CTTTTCTTTCTCTAAG AATCCTCTGGCATTC TGCG CD4mem_ CTCACTCCCATGCTG nm5 TTACAGGTCACCTCT TGCAGGGGCATATTT GATCG CD4mem_ AAATATTACCTATTA nm6 GATTGGTAACAATGA AAAAGACTTGGCAG CCGCCG CD4mem_ CGCCAACAGAGGAT nm7 GGCCAGCCCCACCCC AGAGGACAGCGCAC CCACGGC CD4mem_ CGTTATCAGTAGTTC nm8 TAAACAGCCATAGTA GTCACAGTGCCAGAA GTGAG CD4mem_ GCCGGGCGAGCTGA nm9 GATCAGACAACAGG CGCTGGACGCATCCT AACTACG CD4mem_ GGAAGTCAGAAAGC nm10 TGCTCACTCCATTCC ACTGTGAGAGGGCTT GTCACG CD4mem_ TGTGAGTTAGTTCTA nm11 CAGCACAATGCTTGG CTGCTGTTTCAGCAA TTGCG CD4mem_ CGACTTCCCAGCCAA nm12 GGGAAACTGTCACCG AGGGTGGGACTAAA TCTGAC CD4mem_ CGCGCGCCTATTGAT nm13 TTGTTTCTGAGGAGA GTACACCGTTCACTA TTGTA CD4mem_ TCTGCGTATTCCTTTC nm14 TGTTCTTTAAAAATG TTAAACCATGGGGTG CTCG CD4mem_ CGCCCCACACTGGGG nm15 TCACCCACCTATGAG CGGATCCAGGGGCA CTCTGC CD4mem_ TTCCTCAGCTCCTGT nm16 TCTTGGCCTGAAACC CCACAGCCTTGATGG CAGCG CD4mem_ CGTACAGAGCCTTAA nm17 ACCACATCGTGGCGG TGCCGTCTGAGCTGT AGCGG CD4mem_ CTTTTCCTTGCTAAA nm18 TCAATTCCCTAAGAC ATCAGGACTGTGAGA CATCG CD4mem_ CTCATATAACCCCAA nm19 GAGGTAAATTAGTAT AATTTAACCTACATT ATACG CD4mem_ CAGAAACCTCACACT nm20 CAATTAGCGAGACTG CAAACACTCTGTATT AACCG CD4mem_ CGCCTCCCACCCCTG nm2l GCAGGCTGCCATCTT TGCCAAGCACAGGA GGTCGC CD4mem_ ATCATTGTTCTCTCC nm22 GTGCAGCTAGGTATG CCGCAAGGTCTCGGG TTCCG CD4mem_ CATTTTCCCAAGGGT nm23 CCAGGCCCTAAACAT GCCAGACTACCAGTG GATCG CD4mem_ CGCATTTGAGGAGCT nm24 CTAAGTTGTTGAATC TAAGTTGTTGGATGA GTCAA CD4mem_ CGTTGTCAGGAGCGC nm25 TGGTGGTTTAGGTTC TCCACAGACGCAGG AAAACA CD4mem_ CGCCAACACAGACG nm26 AACCCCAACACGTGG CAAACCCCAACACA GGCGAAC CD4mem_ TCCTCAACATGGTAT nm27 GGGGTTCGCTATCAC CAGCGTGAAGATGG AAAACG CD4mem_ CGATGACTAATTTGG nm28 TTAGCGGCAACAACA GGCTTCTTGCGGCGA GGCCT CD4mem_ CGGCGTGTGTCTTTG nm29 TTGAATGCCTTATTG AGGTCACACACTCTA TGCTT CD4mem_ CGGCCATCCTGCTTT nm30 AGGGATGAATTGAA ACTGGAAAGAGAGT AGTACCA CD4mem_ TGAGAAGGGGCACC nm31 CAATGTGCTTCCTCT TGGGGTGCAGCGGTG TGGCCG CD4mem_ CGCACACACATACTT nm32 GCATGTGGATGCAAA CACAATTGGTGCATG GGTTT CD4mcm_ CGCATCTGAGCGTAG nm33 ACACACAGATCTGAG CTTGGATGGTGGTCA CTGCG CD4mem_ CAGAAGGTCACACA nm34 GACGGTTGCGCTGCT CTCTCACCACTGCAA GCTCCG CD4mem_ CGCCTAGGCTCAAGC nm35 AATCTGGCTCTGGAT GTCTTTAACTTGTGA TTGAA CD4mem_ CGCCTCTCAAGAGCA nm36 CGATGTAAGGGCTCC AAGATGAGTTTGGGC TTCCC CD4mem_ CGGTTAAACATTGGT nm37 ATAGAAACCAGATCT ACTTTTAATTGAAAT CAGAC CD4mem_ CGGAAAAGGAGCTT nm38 GTCTTGAGAAACAAC AAAGAATTGAGCTAT AGTTTC CD4mem_ TGCAGTTAGGACTCC nm39 ATAGCAGGCCTGCAG TGGCCCTGGTGATAA CCTCG CD4mem_ AGGAAGCCTTTAAAG nm40 GACTGGACCCGGAA AGCACCTACTAAAGT GTATCG CD4mem_ CGGTTAATTATGGAA nm41 AAACAGCTTGTTAAG CAAATGCTAATGTAA GAAGA CD4mem_ CGGTGACAGATTTCT nm42 ATCCAGGCCAGATCA AAGTCCGGTGGTTTC GGAAT CD4mem_ CGGTACCTCTACTGC nm43 TGAGTCCAAAGTCAC CGCGGCATACCCAGC TCGGC

TABLE 4F Monocytes-Marker Baso- Eosin- phil phil Marker- Target- Granu- Granu- ID ID SYMBOL Accession locytes locytes MOC_ cg2324 PARK2 NM_0045 0.96 0.96 nm21 4761 62 MOC_ cg1343 MTMR11 NM_1818 0.84 0.84 nm22 0807 73 MOC_ cg0592 TCF7L2 NM_0011 0.79 0.82 nm23 3857 46284 MOC_ cg0104 LDLRAD4 NM_1814 0.76 0.85 nm24 1239 (C18orf1) 82 MOC_ cg2145 ERICH1 NM_2073 0.90 0.92 nm25 9713 32 MOC_ cg1265 EHD4 NM_1392 0.96 0.82 nm26 5112 65 MOC_ cg1048 CENPA NM_0018 0.91 0.86 nm27 0329 09 MOC_ cg1442 MYOF NM_1333 0.94 0.92 nm28 8166 37 MOC_ cg2589 PPM1F NM_0146 0.89 0.85 nm29 8577 34 MOC_ cg1663 FAR1 NM_0322 0.91 0.92 nm30 6767 28 MOC_ cg0224 SCN1A NM_0141 0.89 0.90 nm31 4028 39 MOC_ cg0721 TRRAP NM_0034 0.90 0.91 nm32 3487 96 MOC_ cg0396 MGRN1 NM_0152 0.98 0.97 nm33 3853 46 MOC_ cg2205 RBM47 NM_0190 0.90 0.89 nm34 6336 27 MOC_ cg1806 KIAA0146 NM_0010 0.92 0.91 nm35 6690 80394 MOC_ cg0010 KAZN NM_2016 0.90 0.89 nm36 1629 (KIAA1-26 28 MOC_ cg2091 RIN2 — 0.97 0.97 nm37 8393 MOC_ cg1073  ERCC1 — 0.86 0.81 nm38 2094 ncMOC_ cg0414 ANKRD11 NM_0132 0.88 0.88 nm1 3805 75 ncMOC_ cg0700 ERICH1 NM_2073 0.95 0.94 nm3 4744 32 ncMOC_ cg0736 SECTM1 NM_0030 0.89 0.89 nm6 9606 04 ncMOC_ cg0202 DUSP1 NM_0044 0.93 0.94 nm8 9908 17 ncMOC_ cg1690 — — 0.91 0.86 nm9 8740 ncMOC_ cg0896 — — 0.96 0.94 nm10 9823 nmMOC_ cg1468 — — 0.91 0.90 nm11 4854 ncMOC_ cg2453 — — 0.98 0.97 nm12 4048 ncMOC_ cg1968 CYB561 NM_0010 0.90 0.76 nm13 3800 17917 ncMOC_ cg0837 KCNQ1 NM_0002 0.88 0.79 nm15 6310 18 ncMOC_ cg0745 — — 0.91 0.91 nm19 7429 ncMOC_ cg1049 FANCA NM_0001 0.86 0.89 nm20 2417 35 ncMOC_ cg0174 FAM26F NM_0010 0.91 0.92 nm21 2428 10919 ncMOC_ cg1958 PRKACA NM_2075 0.91 0.93 nm22 6199 18 ncMOC_ cg1014 — — 0.93 0.95 nm24 3416 ncMOC_ cg0326 TSPAN16 NM_0124 0.87 0.77 nm25 3792 66 ncMOC_ cg0977 — — 0.86 0.83 nm26 9405 ncMOC_ cg1628 — — 0.90 0.85 nm27 8101 ncMOC_ cg2038 NAAA NM_0010 0.80 0.81 nm28 0448 42402 ncMOC_ cg0539 ELF5 NM_0014 0.87 0.88 nm29 0144 22 ncMOC_ cg1318 GPR152 NM_2069 0.88 0.88 nm30 7188 97 ncMOC_ cg0432 TCF7L2 NM_0011 0.93 0.90 nm31 2596 46284 ncMOC_ cg0774 UHRF1BP1L NM_0010 0.87 0.88 nm32 4832 06947 ncMOC_ cg1331 DDAH2 NM_0139 0.87 0.80 nm33 8914 74 ncMOC_ cg1443 SMG6 NM_0175 0.87 0.83 nm34 9774 75 ncMOC_ cg1589 — — 0.80 0.72 nm35 6579 ncMOC_ cg0973 LOC285740 NR_0271 0.88 0.75 nm36 6194 13 ncMOC_ cg1889 RGS12 NM_1982 0.89 0.88 nm37 8336 29 ncMOC_ cg0926 TMEM181 NM_0208 0.94 0.95 nm38 2230 23 ncMOC_ cg1079 — — 0.97 0.95 nm39 4991 ncMOC_ cg0266 WIPI2 NM_0160 0.85 0.84 nm40 7577 03 ncMOC_ cg0607 BCL6 NM_0017 0.88 0.69 nm42 0445 06 ncMOC_ cg2414 RASA3 NM_0073 0.86 0.85 nm44 3729 68 ncMOC_ cg1112 WDR46 NM_0054 0.79 0.60 nm46 9609 52 ncMOC_ cg0231 LOC33879 NR_0028 0.80 0.57 nm48 7313 9 09 ncMOC_ cg0469 SNRPC NR_0294 0.89 0.40 nm50 0793 72 Neutro- Non- phil Classical lassical Marker- Granu- Mono- Mono- NK ID locytes cytes cytes classical B-Cells MOC_ 0.97 0.03 0.06 0.97 0.98 nm21 MOC_ 0.86 0.03 0.07 0.89 0.82 nm22 MOC_ 0.81 0.02 0.08 0.92 0.92 nm23 MOC_ 0.77 0.03 0.08 0.93 0.83 nm24 MOC_ 0.94 0.08 0.14 0.91 0.93 nm25 MOC_ 0.68 0.01 0.04 0.97 0.88 nm26 MOC_ 0.84 0.07 0.09 0.94 0.91 nm27 MOC_ 0.85 0.11 0.11 0.95 0.95 nm28 MOC_ 0.73 0.06 0.07 0.84 0.91 nm29 MOC_ 0.91 0.10 0.15 0.92 0.88 nm30 MOC_ 0.86 0.13 0.12 0.88 0.91 nm31 MOC_ 0.91 0.10 0.13 0.90 0.60 nm32 MOC_ 0.97 0.26 0.27 0.97 0.98 nm33 MOC_ 0.87 0.18 0.16 0.85 0.75 nm34 MOC_ 0.91 0.06 0.10 0.91 0.91 nm35 MOC_ 0.84 0.11 0.14 0.88 0.75 nm36 MOC_ 0.90 0.21 0.12 0.98 0.98 nm37 MOC_ 0.76 0.13 0.09 0.87 0.71 nm38 ncMOC_ 0.89 0.82 0.32 0.91 0.88 nm1 ncMOC_ 0.93 0.93 0.39 0.96 0.95 nm3 ncMOC_ 0.93 0.91 0.48 0.95 0.95 nm6 ncMOC_ 0.94 0.92 0.23 0.93 0.93 nm8 ncMOC_ 0.90 0.85 0.18 0.93 0.92 nm9 ncMOC_ 0.94 0.96 0.30 0.95 0.97 nm10 nmMOC_ 0.91 0.91 0.26 0.88 0.88 nm11 ncMOC_ 0.96 0.82 0.18 0.98 0.97 nm12 ncMOC_ 0.85 0.87 0.24 0.93 0.92 nm13 ncMOC_ 0.91 0.81 0.19 0.98 0.94 nm15 ncMOC_ 0.92 0.87 0.29 0.92 0.92 nm19 ncMOC_ 0.90 0.83 0.25 0.88 0.90 nm20 ncMOC_ 0.92 0.91 0.36 0.92 0.93 nm21 ncMOC_ 0.97 0.96 0.45 0.98 0.98 nm22 ncMOC_ 0.94 0.95 0.46 0.95 0.93 nm24 ncMOC_ 0.79 0.85 0.37 0.86 0.85 nm25 ncMOC_ 0.81 0.73 0.25 0.85 0.91 nm26 ncMOC_ 0.85 0.74 0.26 0.88 0.86 nm27 ncMOC_ 0.77 0.83 0.35 0.83 0.83 nm28 ncMOC_ 0.88 0.87 0.42 0.88 0.85 nm29 ncMOC_ 0.88 0.88 0.44 0.95 0.92 nm30 ncMOC_ 0.90 0.92 0.49 0.92 0.91 nm31 ncMOC_ 0.89 0.89 0.48 0.86 0.89 nm32 ncMOC_ 0.84 0.80 0.39 0.89 0.90 nm33 ncMOC_ 0.86 0.87 0.46 0.81 0.89 nm34 ncMOC_ 0.75 0.76 0.36 0.76 0.81 nm35 ncMOC_ 0.85 0.87 0.49 0.91 0.90 nm36 ncMOC_ 0.89 0.85 0.46 0.88 0.88 nm37 ncMOC_ 0.96 0.95 0.57 0.95 0.89 nm38 ncMOC_ 0.97 0.84 0.46 0.96 0.95 nm39 ncMOC_ 0.88 0.85 0.28 0.58 0.66 nm40 ncMOC_ 0.69 0.70 0.18 0.86 0.89 nm42 ncMOC_ 0.84 0.67 0.25 0.86 0.63 nm44 ncMOC_ 0.52 0.58 0.13 0.67 0.82 nm46 ncMOC_ 0.77 0.61 0.21 0.89 0.86 nm48 ncMOC_ 0.77 0.75 0.11 0.85 0.87 nm50 CD4 + CD4 + CD4 + Th Th Marker- Th CD4 + CD4 + Central Effect. ID naive Th1 Th2 Mem. Mem. MOC_ 0.98 0.98 0.99 0.99 0.98 nm21 MOC_ 0.86 0.87 0.90 0.89 0.89 nm22 MOC_ 0.80 0.83 0.84 0.80 0.84 nm23 MOC_ 0.75 0.94 0.95 0.89 0.95 nm24 MOC_ 0.92 0.84 0.90 0.89 0.91 nm25 MOC_ 0.95 0.90 0.80 0.87 0.80 nm26 MOC_ 0.93 0.93 0.94 0.93 0.93 nm27 MOC_ 0.95 0.93 0.95 0.95 0.95 nm28 MOC_ 0.89 0.88 0.88 0.87 0.88 nm29 MOC_ 0.90 0.92 0.92 0.92 0.92 nm30 MOC_ 0.91 0.89 0.88 0.89 0.90 nm31 MOC_ 0.92 0.90 0.89 0.90 0.90 nm32 MOC_ 0.98 0.99 0.98 0.98 0.98 nm33 MOC_ 0.88 0.81 0.83 0.84 0.83 nm34 MOC_ 0.93 0.91 0.92 0.94 0.91 nm35 MOC_ 0.92 0.83 0.86 0.85 0.85 nm36 MOC_ 0.98 0.98 0.98 0.98 0.98 nm37 MOC_ 0.87 0.88 0.88 0.89 0.90 nm38 ncMOC_ 0.90 0.88 0.88 0.89 0.88 nm1 ncMOC_ 0.94 0.96 0.96 0.95 0.97 nm3 ncMOC_ 0.89 0.88 0.89 0.90 0.90 nm6 ncMOC_ 0.93 0.92 0.91 0.89 0.89 nm8 ncMOC_ 0.91 0.88 0.90 0.90 0.90 nm9 ncMOC_ 0.96 0.96 0.95 0.97 0.96 nm10 nmMOC_ 0.91 0.84 0.84 0.86 0.85 nm11 ncMOC_ 0.98 0.97 0.97 0.97 0.98 nm12 ncMOC_ 0.86 0.91 0.92 0.94 0.93 nm13 ncMOC_ 0.84 0.98 0.97 0.98 0.98 nm15 ncMOC_ 0.92 0.92 0.91 0.91 0.90 nm19 ncMOC_ 0.89 0.75 0.73 0.78 0.77 nm20 ncMOC_ 0.92 0.92 0.91 0.93 0.93 nm21 ncMOC_ 0.91 0.97 0.95 0.97 0.98 nm22 ncMOC_ 0.93 0.91 0.92 0.92 0.92 nm24 ncMOC_ 0.88 0.82 0.84 0.86 0.86 nm25 ncMOC_ 0.89 0.89 0.91 0.93 0.91 nm26 ncMOC_ 0.89 0.89 0.89 0.89 0.90 nm27 ncMOC_ 0.84 0.80 0.81 0.82 0.83 nm28 ncMOC_ 0.87 0.75 0.81 0.81 0.81 nm29 ncMOC_ 0.85 0.85 0.86 0.89 0.87 nm30 ncMOC_ 0.92 0.91 0.92 0.93 0.93 nm31 ncMOC_ 0.87 0.87 0.87 0.86 0.89 nm32 ncMOC_ 0.86 0.86 0.86 0.86 0.87 nm33 ncMOC_ 0.87 0.87 0.89 0.87 0.87 nm34 ncMOC_ 0.80 0.79 0.80 0.78 0.81 nm35 ncMOC_ 0.90 0.90 0.89 0.89 0.91 nm36 ncMOC_ 0.88 0.81 0.84 0.84 0.83 nm37 ncMOC_ 0.93 0.95 0.95 0.96 0.96 nm38 ncMOC_ 0.97 0.97 0.97 0.97 0.96 nm39 ncMOC_ 0.89 0.84 0.84 0.82 0.84 nm40 ncMOC_ 0.86 0.86 0.83 0.86 0.87 nm42 ncMOC_ 0.85 0.83 0.84 0.85 0.84 nm44 ncMOC_ 0.80 0.78 0.77 0.79 0.77 nm46 ncMOC_ 0.78 0.87 0.86 0.87 0.86 nm48 ncMOC_ 0.90 0.91 0.93 0.93 0.92 nm50 CD8 + Cyto- Marker- toxic NK ID T-Cells T-Cells Discovery Fragment MOC_ 0.97 0.98 TGGGATGGAACGGCTGC nm21 GACAGATCTCCATTAAA GCCAGCGCGTCGTTCG MOC_ 0.90 0.86 TTCTTGGACCCCTCTTCT nm22 TTGTCCCTTCTTCCTCTT TATCACCCAGAGCG MOC_ 0.90 0.90 CGGCCATCAACCAGATC nm23 CTTGGGCGGAGGGTAGG TGACCTCCCTTCTCAGG MOC_ 0.75 0.89 CGCCGCTCATGGGCCTG nm24 GTGTGCATGCAGCTGCG CAGAGGGCCTCTGCCT MOC_ 0.92 0.89 TTGTGAGGACTGATGGTG nm25 TGGACACCAGCGAGGAA GACCCGACACTGGCCG MOC_ 0.97 0.96 AGAGAAACTCCACGCCC nm26 ACTAACAGTCATTCTCTA TTTCGTTTGCATGCG MOC_ 0.93 0.92 CGATCTTAAGAGAAAGG nm27 GCAGGAGTGTTTCCTTG ACCCCACATTCTCACT MOC_ 0.96 0.95 CGCCCCCGGGGTAGCGG nm28 CTCTCGTTCTGATAGACT TCATCAGTGAACTCC MOC_ 0.92 0.89 CGCTGATCCAGTCACCG nm29 GGGAGGGGCTGACTGGC AGCCACACAGAGGTTT MOC_ 0.90 0.90 CGGTTCCCAATTTGAAG nm30 AGTGGAGACAGAAGTCA AGAAAATAAGCTTTTC MOC_ 0.91 0.88 CGGCTCAGCCTTATTGTC nm31 TTGCTTAATGTCTGGGTC TCAGTTTTAGAGAC MOC_ 0.92 0.92 TGTGAAGCAGCTAGAGG nm32 CGCGCTGGAAACCTGAT ATGCTGCTGCCTCG MOC_ 0.97 0.98 TGGCCACGGGTCATTCG nm33 TGGTTCCCCTGGAGCCTT GCGGTGTATAGAGCG MOC_ 0.87 0.82 CGTGAACTTCCTAGAGG nm34 CCAAAGTAAAAATAAAA ACAGGGTCGCTAACAT MOC_ 0.92 0.91 CGGAAGGTGAGTGGGCA nm35 ATGAAATGTCCAATTTT AAAAGAAATTCCACGT MOC_ 0.86 0.69 CGCAAGAATGCACTTAG nm36 TTAATCCAACAAGTATTT ATTCAGTGCCTGAGT MOC_ 0.98 0.98 TTTCAACAACACCACTG nm37 AAAGAATGTAAACGGAG CTGGTCGCGTTGGTCG MOC_ 0.90 0.87 GAGGAAGTCCTTTCTGG nm38 AGTCTGACCCTCAGTCT GCCTGCTTCAAATGCG ncMOC_ 0.89 0.87 CGAAATCAGCGGAGGCC nm1 CCTGCTGAGTGAGTGGA CACACCCAGGCGCACG ncMOC_ 0.96 0.95 AACATGAGCAGCATGGA nm3 CAACGCGGTACAACGGG GCGAGAGCGCCAACCG ncMOC_ 0.93 0.88 CGCAGGCTTGGAGCCAT nm6 GCCAGTGACACGCCTAG GAAAGTTCACGCACCG ncMOC_ 0.94 0.88 CCCACTATATATTGGTCC nm8 CGAATGTGCTGAGTTCA GCAAATGTCTTGACG ncMOC_ 0.91 0.89 CGGAAGAACACTTGTAT nm9 ATGCTGACATCAGCAAG CAAAATGCATACAGTT ncMOC_ 0.96 0.95 GGCTTCCGGTGACCAGG nm10 ATAGGAAGTGTTGCAGG CCCTGCCCCGAGGGCG nmMOC_ 0.89 0.84 CGCCGAGCTCAGCAGAA nm11 ACCCGCCCAGAAGGTCA AGGACCAGCAAAAGGG ncMOC_ 0.98 0.98 GAGGCCTGGCACGGCGG nm12 CACCGGAAGCGGGTACT GGTGCCCTAAGGAGCG ncMOC_ 0.94 0.91 TGCGGGCCTCTCCTGCCC nm13 TTTGTACTCCACGAGGT GTGAGGAAGTTGCCG ncMOC_ 0.98 0.97 CGCGCTCACAGCCTCCG nm15 TTCCCAGACACGCCCGG GCCTGAGCCCCCAGGC ncMOC_ 0.93 0.90 CGGTCATAGTCCTCTGG nm19 AGTPGACATCAGTGGGA CCTCGGTGAAACTGCA ncMOC_ 0.87 0.86 CGCTGTCCGGAACTGGG nm20 GTGCTCCACCCACACTG TCTGGAACTGGCACAG ncMOC_ 0.92 0.94 CGCCCATCATAGAAGTA nm21 CCAGAACTTGAGCTGGA CTTTGCTGATTTAGCT ncMOC_ 0.97 0.97 CGCGGTTGCGCTAAGGG nm22 GAGAGCTGCCTTGATAA GACCTCTTGGGCACCC ncMOC_ 0.91 0.85 TGGGGAAGTCGCTGCTG nm24 AGAACTCCGATGCCAAG CGCTGACCCAGCCTCG ncMOC_ 0.87 0.76 TGAATGGATCCAGAGGC nm25 TCTGTGATGCAGAAATC TAGCTACAAGCCACCG ncMOC_ 0.91 0.86 CGTAATGATCTTGAGGA nm26 AGAAAGAAAATGCAAA GGGAAGTATGAAATAGC ncMOC_ 0.90 0.89 CGGTCTAATTAAAATAG nm27 GGAACAAGAACCAAAA AATCCCCTAGTTCCAGG ncMOC_ 0.84 0.79 CGGTGGAGTTCGGAGCA nm28 ATTTTTTGCAGGCAGGA AGTGGATCTTACAAAG ncMOC_ 0.83 0.72 CGGGCCAAATCATCACT nm29 GGGCAGAACTAGGCCAT AGGGTGCAAAATATAG ncMOC_ 0.87 0.73 CGCCCCATAGGAAGTAG nm30 TAGAAGCGGCAGGCAGC TGTCCCCACTCGGCCAG ncMOC_ 0.91 0.87 GGCCATAGTCACACCAA nm31 CAGTCAAACAGGAATCG TCCCAGAGTGATGTCG ncMOC_ 0.87 0.80 CGGCCTCCTTAGAATGTT nm32 TTAAGAATCGGCCATTA ACTCCTGTGCTTGCT ncMOC_ 0.91 0.85 CTCAGCTGTGGGGGCGT nm33 GTGCTGAGCACCAAGCA GAGGGAGCTGAGCCCG ncMOC_ 0.89 0.85 GCCAAATGACTGTGTTG nm34 GCCTATGGGTGACCTGG CCCCTGGCTAGAATCG ncMOC_ 0.82 0.73 CTGGATGGCAGACAGTG nm35 CGTGCAAGCATCACAGC CCACTGGAAGAGGCCG ncMOC_ 0.90 0.86 TTCTTCAAAACCCTAGTC nm36 AGATATTGTTACTTCACT GAAAACTCTCACCG ncMOC_ 0.83 0.76 TGGCTGATGTCTGCTGA nm37 ACACCCGATCATTCACT CAACAGACAGCTCTCG ncMOC_ 0.96 0.95 AGGTCAGCAGACGGTCA nm38 CCGGGGAAAGCATCCAG GCATCTTGTCGCCTCG ncMOC_ 0.98 0.97 CGAGGAGTTGCACTCTA nm39 GCTGCCGTGCCAGCAGT CTCGTCTGCTGTGACG ncMOC_ 0.74 0.78 CGGACTGACTGAACTTG nm40 ACCTGTGACCTCTGACC CGGGGAGCAGAGAACA ncMOC_ 0.89 0.88 CGTGCTGTAGAACATGC nm42 AAGACAGCACCCTGATG TGGGTGAATCTCATTT ncMOC_ 0.81 0.83 GGTCGTGACCCTGCCTC nm44 CACCCTGTGTAAAGTCA CAGCTGCAGGATCTCG ncMOC_ 0.83 0.77 CTGACAAGGGCAGAGGC nm46 ACAAGCAGGAGGGTGCA GCCTGTGGAAGGCCCG ncMOC_ 0.83 0.87 GGGGATGCCGGCGACTC nm48 AGTAGTAAGGCAAGTCC TGCCACCTCCTGGCCG ncMOC_ 0.91 0.91 CGGGGCACAGTTAACTT nm50 ACCCCTTAGGACCAGGA AGTAATCTTTGTGGTA

TABLE 4G Granolucytes and Subtypes Marker Baso- Eosino- phil phil Marker- Target- Granu- Granu- ID ID SYMBOL Accession locytes locytes GRC_ cg1501 TIMP2 NM_003255 0.22 0.09 nm38 0903 GRC_ cg1101 DCP1A NM_018403 0.06 0.09 nm39 4468 GRC_ cg0746 — — 0.09 0.07 nm40 8327 GRC_ cg2128 PCMTD1 NM_052937 0.18 0.08 nm41 5555 GRC_ cg0811 PXT1 NM_152990 0.06 0.01 nm42 0693 GRC_ cg1359 — — 0.11 0.06 nm43 5556 GRC_ cg0342 LOC339524 NR_026986 0.01 0.07 nm44 3077 GRC_ cg0012 UNKL NM_023076 0.14 0.13 nm45 1045 GRC_ cg0730 PVT1 NR_003367 0.05 0.05 nm46 5933 GRC_ cg2366 — — 0.09 0.08 nm47 1721 GRC_ cg0616 — — 0.10 0.11 nm48 8950 GRC_ cg0843 SLC23A2 NM_005116 0.02 0.11 nm49 5683 GRC_ cg0033 PDE4D NM_001165899 0.12 0.05 nm50 5124 GRC_ cg0652 NUDT3 NM_006703 0.31 0.06 nm51 6020 GRC_ cg0382 MTIF2 NM_002453 0.08 0.27 nm52 0688 GRC_ cg1503 GTPDP1 NM_004286 0.14 0.11 nm53 4267 GRC_ cg0140 ANAPC10 NM_014885 0.37 0.06 nm54 0750 GRC_ cg2441 RRM2 NM_001034 0.16 0.09 nm55 9094 GRC_ cg1131 HNRNPUL1 NM_007040 0.31 0.11 nm56 3468 GRC_ cg0070 NCK2 NM_003581 0.67 0.07 nm57 5730 GRC_ cg1560 TTN NM_133378 0.43 0.09 nm58 9237 GRC_ cg1951 UBE2H NM_003344 0.65 0.08 nm59 3582 GRC_ cg1068 ZNF148 NM_021964 0.05 0.12 nm60 7936 GRC_ cg1816 REC8 NM_ 0.06 0.10 nm61 8663 001048205 GRC_ cg2681 MAP7 NM_003980 0.13 0.12 nm62 4100 GRC_ cg1069 NCAPD2 NM_014865 0.08 0.16 nm63 2528 GRC_ cg0512 GLB1 NM_ 0.12 0.17 nm64 0113 001135602 GRC_ cg0179 VPS53 NM_018289 0.31 0.12 nm65 9818 GRC_ cg0272 GRK4 NM_ 0.55 0.06 nm66 2672 001004057 GRC_ cg0699 TRPS1 NM_014112 0.03 0.11 nm67 767 GRC_ cg0557 CHD7 NM_017780 0.38 0.09 nm68 639 GRC_ cg1856 COL18A1 NM_130444 0.62 0.11 nm69 618 GRC_ cg0568 — — 0.07 0.08 nm70 528 GRC_ cg1195 RNF103 NM_005667 0.27 0.14 nm71 8668 GRC_ cg1454 RCOR1 NM_015156 0.63 0.11 nm72 3285 GRC_ cg2083 VKORC1L1 NM_173517 0.06 0.18 nm73 212 GRC_ cg2564 VKORC1L1 NM_173517 0.07 0.18 nm74 3253 GRC_ cg1928 — — 0.10 0.17 nm75 2952 GRC_ cg2455 — — 0.06 0.16 nm76 9796 GRC_ cg0886 PBX1 NM_002585 0.05 0.06 nm77 4944 GRC_ cg1341 ZNF609 NM_015042 0.17 0.20 nm78 6889 GRC_ cg2176 C6orf70 NM_018341 0.44 0.13 nm79 2728 GRC_ cg1159 — — 0.16 0.05 nm80 6902 GRC_ cg1123 CDK5RAP1 NM_016082 0.60 0.04 nm81 1701 GRC_ cg2664 PILRB NM_175047 0.65 0.15 nm82 7135 GRC_ cg0726 AMPD3 NM_ 0.57 0.08 nm83 8332 001025389 GRC_ cg1993 MATN2 NM_030583 0.76 0.10 nm84 5471 GRC_ cg0850 — — 0.09 0.11 nm85 5883 bGRC_ cg0232 HDC NM_002112 0.06 0.84 nm1 9886 bGRC_ cg2667 MCC NM_002387 0.02 0.90 nm2 6468 bGRC_ cg0178 ERI3 NM_024066 0.03 0.75 nm3 2059 bGRC_ cg1264 TTLL8 NM_ 0.03 0.87 nm4 6067 001080447 bGRC_ cg0501 ZFPM1 NM_153813 0.04 0.88 nm5 2676 bGRC_ cg1730 TFB1M; NM_016020 0.05 0.87 nm6 6637 CLDN20 bGRC_ cg2219 MS4A2 NM_ 0.05 0.81 nm7 7708 001142303 bGRC_ cg0352 DENND3 NM_014957 0.09 0.81 nm8 0003 bGRC_ cg1664 DLC1 NM_182643 0.06 0.59 nm9 3422 bGRC_ cg1828 MAS1L NM_052967 0.08 0.82 nm10 1744 bGRC_ cg0786 MAD1L1 NM_003550 0.16 0.92 nm11 2744 bGRC_ cg0355 PFKFB3 NM_ 0.08 0.81 nm12 5710 001145443 bGRC_ cg2405 — — 0.05 0.69 nm13 7792 bGRC_ cg2661 — — 0.05 0.84 nm14 3070 bGRC_ cg2413 TBCD NM_005993 0.04 0.88 nm15 0568 bGRC_ cg04491 PFKFB4 NM_004567 0.06 0.80 nm16 8104 bGRC_ cg1203 DPYSL2 NM_001386 0.07 0.84 nm17 7509 bGRC_ cg1129 — — 0.08 0.92 nm18 4011 bGRC_ cg0275 FBXL14 NM_152441 0.04 0.71 nm19 2529 bGRC_ cg0242 SFSWAP NM_004592; 0.05 0.75 nm20 6739 NM_001261411 bGRC_ cg1208 ADK NM_001123 0.09 0.89 nm21 7639 bGRC_ cg1031 NFAT5 NM_138714 0.04 0.60 nm22 9857 bGRC_ cg2171 — — 0.06 0.78 nm23 5896 bGRC_ cg1420 MEGF9 NM_ 0.08 0.82 nm24 0678 001080497 bGRC_ cg2096 SIK2 NM_015191 0.04 0.80 nm25 4248 bGRC_ cg0338 — — 0.07 0.85 nm26 0342 bGRC_ cg0781 WDFY2 NM_052950 0.05 0.64 nm27 8422 bGRC_ cg2363 — — 0.07 0.84 nm28 9055 bGRC_ cg0008 — — 0.11 0.88 nm29 6283 bGRC_ cg1201 TES NM_015641 0.06 0.84 nm30 8521 bGRC_ cg1248 C1orf198 NM_ 0.12 0.88 nm31 6498 001136494 bGRC_ cg1969 SDPR NM_004657 0.07 0.88 nm32 9264 bGRC_ cg0586 MAP2K4 NM_003010 0.08 0.75 nm33 5769 bGRC_ cg1180 TANCI NM_033394 0.08 0.76 nm34 9342 bGRC_ cg0280 ANXA13 NM_ 0.05 0.80 nm35 0334 001003954 bGRC_ cg0915 ZNF366 NM_152625 0.09 0.90 nm36 1061 bGRC_ cg1463 SHB NM_003028 0.05 0.78 nm37 3252 bGRC_ cg0947 ABCC1 NM_019862 0.07 0.73 nm38 3249 bGRC_ cg1997 LPP NM_005578 0.07 0.63 nm39 5917 bGRC_ cg0238 LIN7A;  NM_004664 0.08 0.63 nm40 7491 MIR617 bGRC_ cg2414 TECR NM_138501 0.08 0.66 nm41 3196 bGRC_ cg2260 — — 0.07 0.88 nm42 9618 bGRC_ cg2479 — — 0.09 0.85 nm43 1846 bGRC_ cg1033 — — 0.06 0.65 nm44 0847 bGRC_ cg0498 ROR1 NM_005012 0.13 0.90 nm45 8216 bGRC_ cg2600 — — 0.06 0.78 nm46 9797 bGRC_ cg2473 — — 0.08 0.82 nm47 6010 bGRC_ cg0465 ARID5B NM_032199 0.09 0.70 nm48 7468 bGRC_ cg0402 RGL1 NM_015149 0.10 0.69 nm49 3434 bGRC_ cg1519 CPB2 NM_016413 0.09 0.82 nm50 2986 eGRC_ cg1509 RPS6KA2 NM_ 0.97 0.16 nm2 0899 001006932 eGRC_ cg2076 TIMP2 NM_003255 0.74 0.13 nm3 1853 eGRC_ cg1190 ANXA11 NM_145868 0.92 0.13 nm4 0509 eGRC_ cg0326 ATL2 NM_022374 0.52 0.14 nm5 9757 eGRC_ cg0941 C10orf18 NM_017782 0.82 0.13 nm6 1597 eGRC_ cg1387 BBX NM_020235 0.81 0.22 nm7 2812 eGRC_ cg2123 — — 0.80 0.17 nm8 7481 eGRC_ cg2306 FARSA NM_004461 0.85 0.18 nm9 0513 eGRC_ cg0874 CALU NM_001219 0.81 0.15 nm10 2095 eGRC_ cg2201 C6orf89 NM_152734 0.88 0.16 nm11 1526 eGRC_ cg2452 PPP1R1B NM_181505 0.85 0.16 nm12 0381 eGRC_ cg10451 — — 0.54 0.21 nm13 4864 eGRC_ cg1038 HEXA NM_000520 0.62 0.14 nm14 7956 eGRC_ cg1889 ETSI NM_ 0.86 0.16 nm15 8103 001143820 eGRC_ cg0000 — — 0.78 0.19 nm16 6459 eGRC_ cg2024 MEF2A NM_ 0.68 0.18 nm17 0243 001130927 eGRC_ cg2399 IGF1R NM_000875 0.86 0.17 nm18 0557 eGRC_ cg1978 C12orf43 NM_022895 0.79 0.18 nm19 8934 eGRC_ cg1166 HEXA NM_000520 0.87 0.19 nm20 8148 eGRC_ cg1638 IL1RL1 NM_016232 0.56 0.18 nm21 6158 eGRC_ cg2623 TMEM220 NM_ 0.69 0.18 nm22 4644 001004313 eGRC_ cg2538 — — 0.71 0.18 nm23 1747 eGRC_ ecg2222 PCYT1A NM_005017 0.57 0.16 nm24 1575 eGRC_ cg1131 MARCH3 NM_178450 0.60 0.21 nm25 0939 eGRC_ cg0959 — — 0.82 0.20 nm26 6645 eGRC_ cg0039 LOC100 NM_ 0.70 0.17 nm27 1067 271715 001145451 eGRC_ cg0183 C7orf36 NM_020192 0.74 0.15 nm28 5368 eGRC_ cg1679 — — 0.74 0.16 nm29 7699 eGRC_ cg1395 USP20 NM_ 0.61 0.20 nm30 3978 001110303 eGRC_ cg1757 OSTal- NM_152672 0.98 0.11 nm31 2056 pha eGRC_ cg0483 — — 0.98 0.15 nm32 6151 eGRC_ cg0280 PCYT1A NM_005017 0.97 0.21 nm33 3925 eGRC_ cg0042 RREB1 NM_ 0.87 0.12 nm34 1164 001003700 eGRC_ cg0369 DKFZp7 NM_138368 0.89 0.17 nm35 5871 61E198 eGRC_ cg2692 EIF4EBP1 NM_004095 0.77 0.10 nm36 1611 eGRC_ cg1517 TMED3 NM_007364 0.82 0.21 nm37 1342 eGRC_ cg0573 HTT NM_002111 0.89 0.22 nm38 6642 eGRC_ cg2303 — — 0.86 0.14 nm39 9807 eGRC_ cg0412 — — 0.41 0.12 nm40 8967 eGRC_ cg1118 MAN2A2 NM_006122 0.98 0.27 nm41 3227 eGRC_ cg2303 DCAF5 NM_003861 0.89 0.16 nm42 7469 eGRC_ cg2557 CHD7 NM_017780 0.85 0.20 nm43 8728 eGRC_ cg1291 MAT2B NM_182796 0.73 0.21 nm44 0830 eGRC_ cg0807 PRKCH NM_006255 0.74 0.20 nm45 7807 eGRC_ cg1420 TMEM156 NM_024943 0.75 0.21 nm46 9186 eGRC_ cg0507 APLP2 NR_024516 0.58 0.23 nm47 8091 eGRC_ cg1976 STX3 NM_004177 0.87 0.24 nm48 4973 eGRC_ cg2520 TSNAX- NR_028394 0.89 0.25 nm49 3627 DISC1 eGRC_ cg2210 DMXL1 NM_005509 0.89 0.26 nm50 6847 eGRC_ cg1796 — — 0.90 0.28 nm51 0717 nGRC_ cg0314 NADSYN1 NM_018161 0.98 0.88 nm1 6219 nGRC_ cg1378 ENO1 NM_001428 0.95 0.78 nm3 5123 nGRC_ cg2381 MCF2L2 NM_015078 0.95 0.69 nm4 9411 GRC_18 cg2560 HIPK3 NM_001048200 0.91 0.77 nm 0606 nGRC_ cg2507 MARCH8 NM_001002265 0.90 0.56 nm7 4794 nGRC_ cg1361 FAM125B NM_033446 0.88 0.76 nm8 8969 nGRC_ cg2605 — — 0.93 0.68 nm9 6277 nGRC_ cg1115 RPTOR NM_001163034 0.97 0.85 nm10 3071 nGRC_ cg0149 RPTOR NM_001163034 0.86 0.76 nm11 8832 nGRC_ cg2109 VPS53 NM_018289 0.91 0.87 nm12 0866 nGRC_ cg0597 CHST15 NM_015892 0.93 0.66 nm13 1678 nGRC_ cg0969 MED21 NM_004264 0.87 0.75 nm15 4051 nGRC_ cg2413 CPM NM_001874 0.96 0.91 nm16 1359 nGRC_ cg1398 ITGAE NM_002208 0.97 0.75 nm17 4928 nGRC_ cg1346 ANKFY1 NM_016376 0.90 0.72 nm20 8144 nGRC_ cg0169 ARG1 NM_000045 0.91 0.74 nm22 9630 nGRC_ cg1093 PCYOX1 NM_016297 0.90 0.85 nm24 4870 nGRC_ cg2639 KLF11 NM_003597 0.83 0.75 nm25 6370 nGRC_ cg2569 SH3PXD2B NM_ 0.90 0.75 nm26 3317 001017995 nGRC_ cg1203 — — 0.95 0.77 nm28 1275 nGRC_ cg2312 DIP2C NM_014974 0.85 0.51 nm29 8584 nGRC_ cg0227 — — 0.87 0.74 nm30 9108 nGRC_ cg2575 — — 0.92 0.76 nm31 7820 nGRC_ cg0646 CAST NM_001750 0.76 0.59 nm32 5076 nGRC_ cg2751 CSGAL NR_024040 0.87 0.67 nm33 0066 NACT1 nGRC_ cg0678 CSGAL NR_024040 0.83 0.79 nm34 4232 NACT1 nGRC_ cg0104 INPP5A NM_005539 0.85 0.51 nm35 0749 nGRC_ cg0710 FOXN3 NM_005197 0.88 0.72 nm36 2397 nGRC_ cg1363 — — 0.82 0.67 nm37 3625 nGRC_ cg2333 — — 0.87 0.83 nm38 8668 nGRC_ cg2240 RGL1 NM_015149 0.87 0.78 nm39 0420 nGRC_ cg2473 — — 0.86 0.54 nm40 7761 nGRC_ cg2391 — — 0.87 0.81 nm41 1433 nGRC_ cg0901 — — 0.87 0.79 nm42 0699 nGRC_ cg0663 MLLT1 NM_005934 0.92 0.79 nm43 3438 nGRC_ cg1600 DCAF4L1 NM_ 0.94 0.73 nm44 0989 001029955 nGRC_ cg0361 HDLBP NM_203346 0.84 0.57 nm45 0527 nGRC_ cg1741 C12orf71 NM_  0.89 0.67 nm46 9815 001080406 nGRC_ cg0605 NKTR NM_005385 0.75 0.71 nm47 9360 nGRC_ cg0705 PEX5 NM_  0.86 0.73 nm48 2231 001131023 nGRC_ cg0236 NQO2 NM_000904 0.96 0.79 nm49 8812 nGRC_ cg0541 — — 0.88 0.66 nm50 8105 Neutro- phil Non- Marker- Granu- Classical Classical NK ID locytes Monocytes Monocytes classical B-Cells GRC_ 0.10 0.85 0.87 0.89 0.87 nm38 GRC_ 0.09 0.93 0.91 0.91 0.91 nm39 GRC_ 0.12 0.76 0.82 0.87 0.87 nm40 GRC_ 0.05 0.78 0.80 0.78 0.87 nm41 GRC_ 0.20 0.72 0.77 0.88 0.87 nm42 GRC_ 0.04 0.68 0.77 0.87 0.91 nm43 GRC_ 0.15 0.67 0.74 0.90 0.91 nm44 GRC_ 0.11 0.67 0.74 0.81 0.85 nm45 GRC_ 0.04 0.56 0.63 0.77 0.74 nm46 GRC_ 0.06 0.53 0.65 0.90 0.89 nm47 GRC_ 0.12 0.61 0.64 0.83 0.87 nm48 GRC_ 0.49 0.95 0.94 0.95 0.96 nm49 GRC_ 0.05 0.76 0.84 0.34 0.91 nm50 GRC_ 0.05 0.80 0.83 0.90 0.90 nm51 GRC_ 0.16 0.80 0.82 0.90 0.89 nm52 GRC_ 0.33 0.84 0.84 0.85 0.87 nm53 GRC_ 0.03 0.78 0.81 0.87 0.86 nm54 GRC_ 0.25 0.79 0.80 0.87 0.87 nm55 GRC_ 0.06 0.74 0.84 0.89 0.87 nm56 GRC_ 0.04 0.87 0.89 0.89 0.89 nm57 GRC_ 0.16 0.79 0.87 0.95 0.66 nm58 GRC_ 0.13 0.90 0.89 0.81 0.94 nm59 GRC_ 0.58 0.84 0.86 0.90 0.92 nm60 GRC_ 0.26 0.73 0.74 0.71 0.84 nm61 GRC_ 0.28 0.73 0.82 0.92 0.92 nm62 GRC_ 0.61 0.86 0.89 0.87 0.90 nm63 GRC_ 0.45 0.81 0.83 0.89 0.89 nm64 GRC_ 0.42 0.86 0.85 0.89 0.90 nm65 GRC_ 0.25 0.82 0.90 0.93 0.95 nm66 GRC_ 0.21 0.64 0.73 0.43 0.76 nm67 GRC_ 0.17 0.78 0.78 0.86 0.52 nm68 GRC_ 0.21 0.88 0.85 0.90 0.97 nm69 GRC_ 0.16 0.63 0.71 0.77 0.77 nm70 GRC_ 0.65 0.89 0.91 0.81 0.92 nm71 GRC_ 0.10 0.82 0.83 0.86 0.87 nm72 GRC_ 0.64 0.82 0.86 0.89 0.90 nm73 GRC_ 0.65 0.82 0.82 0.86 0.86 nm74 GRC_ 0.54 0.82 0.80 0.88 0.69 nm75 GRC_ 0.55 0.76 0.81 0.87 0.86 nm76 GRC_ 0.05 0.63 0.51 0.14 0.76 nm77 GRC_ 0.67 0.86 0.88 0.84 0.90 nm78 GRC_ 0.14 0.73 0.80 0.93 0.92 nm79 GRC_ 0.05 0.59 0.61 0.88 0.91 nm80 GRC_ 0.09 0.74 0.78 0.78 0.78 nm81 GRC_ 0.18 0.84 0.85 0.88 0.88 nm82 GRC_ 0.14 0.74 0.78 0.86 0.50 nm83 GRC_ 0.10 0.85 0.79 0.84 0.80 nm84 GRC_ 0.39 0.67 0.74 0.87 0.90 nm85 bGRC_ 0.90 0.91 0.89 0.90 0.91 nm1 bGRC_ 0.96 0.96 0.95 0.95 0.96 nm2 bGRC_ 0.97 0.96 0.96 0.97 0.96 nm3 bGRC_ 0.96 0.95 0.95 0.95 0.96 nm4 bGRC_ 0.96 0.96 0.95 0.95 0.96 nm5 bGRC_ 0.89 0.88 0.90 0.90 0.92 nm6 bGRC_ 0.91 0.90 0.89 0.88 0.89 nm7 bGRC_ 0.90 0.92 0.91 0.90 0.91 nm8 bGRC_ 0.86 0.86 0.86 0.87 0.85 nm9 bGRC_ 0.89 0.90 0.90 0.57 0.86 nm10 bGRC_ 0.93 0.91 0.92 0.93 0.93 nm11 bGRC_ 0.96 0.97 0.97 0.97 0.98 nm12 bGRC_ 0.93 0.94 0.91 0.93 0.93 nm13 bGRC_ 0.92 0.92 0.92 0.92 0.91 nm14 bGRC_ 0.92 0.85 0.78 0.94 0.76 nm15 bGRC_ 0.91 0.90 0.91 0.84 0.93 nm16 bGRC_ 0.92 0.93 0.91 0.93 0.92 nm17 bGRC_ 0.94 0.93 0.93 0.91 0.93 nm18 bGRC_ 0.89 0.90 0.90 0.89 0.89 nm19 bGRC_ 0.91 0.92 0.91 0.61 0.84 nm20 bGRC_ 0.95 0.92 0.92 0.91 0.93 nm21 bGRC_ 0.91 0.91 0.88 0.90 0.89 nm22 bGRC_ 0.88 0.90 0.87 0.90 0.91 nm23 bGRC_ 0.91 0.89 0.89 0.90 0.90 nm24 bGRC_ 0.90 0.85 0.85 0.89 0.88 nm25 bGRC_ 0.91 0.91 0.90 0.90 0.89 nm26 bGRC_ 0.92 0.92 0.91 0.90 0.91 nm27 bGRC_ 0.90 0.90 0.90 0.89 0.88 nm28 bGRC_ 0.94 0.95 0.94 0.94 0.93 nm29 bGRC_ 0.90 0.90 0.88 0.65 0.90 nm30 bGRC_ 0.94 0.93 0.93 0.95 0.95 nm31 bGRC_ 0.92 0.90 0.91 0.92 0.90 nm32 bGRC_ 0.91 0.92 0.89 0.90 0.90 nm33 bGRC_ 0.91 0.92 0.91 0.89 0.91 nm34 bGRC_ 0.88 0.88 0.86 0.87 0.88 nm35 bGRC_ 0.92 0.92 0.91 0.90 0.89 nm36 bGRC_ 0.89 0.81 0.80 0.90 0.90 nm37 bGRC_ 0.88 0.90 0.89 0.90 0.90 nm38 bGRC_ 0.90 0.91 0.90 0.89 0.91 nm39 bGRC_ 0.92 0.91 0.91 0.90 0.92 nm40 bGRC_ 0.91 0.93 0.93 0.78 0.92 nm41 bGRC_ 0.87 0.91 0.88 0.88 0.79 nm42 bGRC_ 0.91 0.89 0.89 0.92 0.90 nm43 bGRC_ 0.90 0.91 0.89 0.73 0.89 nm44 bGRC_ 0.91 0.94 0.94 0.92 0.92 nm45 bGRC_ 0.86 0.89 0.87 0.87 0.88 nm46 bGRC_ 0.91 0.91 0.91 0.89 0.90 nm47 bGRC_ 0.88 0.91 0.87 0.89 0.89 nm48 bGRC_ 0.92 0.90 0.93 0.90 0.89 nm49 bGRC_ 0.88 0.89 0.87 0.90 0.87 nm50 eGRC_ 0.83 0.95 0.96 0.78 0.97 nm2 eGRC_ 0.61 0.93 0.94 0.91 0.93 nm3 eGRC_ 0.62 0.98 0.98 0.97 0.84 nm4 eGRC_ 0.78 0.88 0.87 0.93 0.92 nm5 eGRC_ 0.61 0.87 0.86 0.88 0.74 nm6 eGRC_ 0.95 0.95 0.95 0.96 0.96 nm7 eGRC_ 0.76 0.87 0.87 0.93 0.92 nm8 eGRC_ 0.54 0.83 0.89 0.93 0.97 nm9 eGRC_ 0.57 0.89 0.92 0.88 0.91 nm10 eGRC_ 0.59 0.85 0.86 0.90 0.89 nm11 eGRC_ 0.73 0.86 0.89 0.90 0.87 nm12 eGRC_ 0.93 0.94 0.93 0.92 0.94 nm13 eGRC_ 0.81 0.84 0.84 0.85 0.89 nm14 eGRC_ 0.53 0.87 0.84 0.89 0.88 nm15 eGRC_ 0.87 0.90 0.89 0.89 0.90 nm16 eGRC_ 0.91 0.87 0.85 0.87 0.85 nm17 eGRC_ 0.59 0.86 0.90 0.88 0.89 nm18 eGRC_ 0.70 0.86 0.84 0.86 0.86 nm19 eGRC_ 0.87 0.89 0.86 0.87 0.89 nm20 eGRC_ 0.83 0.91 0.92 0.74 0.89 nm21 eGRC_ 0.70 0.75 0.73 0.91 0.85 nm22 eGRC_ 0.85 0.86 0.83 0.86 0.87 nm23 eGRC_ 0.82 0.82 0.81 0.85 0.79 nm24 eGRC_ 0.89 0.91 0.88 0.89 0.90 nm25 eGRC_ 0.85 0.83 0.84 0.86 0.84 nm26 eGRC_ 0.72 0.76 0.77 0.88 0.83 nm27 eGRC_ 0.58 0.71 0.73 0.80 0.86 nm28 eGRC_ 0.66 0.74 0.76 0.74 0.75 nm29 eGRC_ 0.83 0.86 0.85 0.83 0.87 nm30 eGRC_ 0.27 0.95 0.98 0.98 0.98 nm31 eGRC_ 0.49 0.84 0.86 0.98 0.98 nm32 eGRC_ 0.95 0.99 0.99 0.98 0.98 nm33 eGRC_ 0.39 0.86 0.87 0.91 0.90 nm34 eGRC_ 0.51 0.84 0.91 0.93 0.94 nm35 eGRC_ 0.47 0.71 0.79 0.88 0.91 nm36 eGRC_ 0.77 0.93 0.92 0.92 0.93 nm37 eGRC_ 0.82 0.92 0.92 0.92 0.92 nm38 eGRC_ 0.45 0.73 0.79 0.90 0.90 nm39 eGRC_ 0.83 0.79 0.82 0.90 0.83 nm40 eGRC_ 0.75 0.98 0.98 0.98 0.98 nm41 eGRC_ 0.44 0.86 0.87 0.89 0.90 nm42 eGRC_ 0.78 0.91 0.89 0.92 0.88 nm43 eGRC_ 0.87 0.91 0.90 0.91 0.92 nm44 eGRC_ 0.92 0.92 0.93 0.82 0.93 nm45 eGRC_ 0.76 0.88 0.87 0.92 0.92 nm46 eGRC_ 0.92 0.93 0.93 0.92 0.93 nm47 eGRC_ 0.87 0.91 0.90 0.91 0.90 nm48 eGRC_ 0.80 0.89 0.91 0.92 0.88 nm49 eGRC_ 0.82 0.90 0.91 0.90 0.91 nm50 eGRC_ 0.87 0.92 0.89 0.93 0.91 nm51 nGRC_ 0.07 0.97 0.98 0.97 0.97 nm1 nGRC_ 0.04 0.88 0.92 0.96 0.97 nm3 nGRC_ 0.03 0.78 0.86 0.96 0.94 nm4 GRC_18 0.04 0.87 0.87 0.92 0.92 nm nGRC_ 0.04 0.83 0.90 0.95 0.95 nm7 nGRC_ 0.03 0.89 0.91 0.90 0.89 nm8 nGRC_ 0.05 0.80 0.84 0.96 0.95 nm9 nGRC_ 0.06 0.60 0.77 0.97 0.97 nm10 nGRC_ 0.12 0.61 0.70 0.86 0.89 nm11 nGRC_ 0.07 0.92 0.93 0.88 0.91 nm12 nGRC_ 0.04 0.61 0.73 0.97 0.96 nm13 nGRC_ 0.01 0.80 0.84 0.88 0.83 nm15 nGRC_ 0.13 0.94 0.98 0.96 0.96 nm16 nGRC_ 0.04 0.58 0.61 0.85 0.97 nm17 nGRC_ 0.04 0.90 0.91 0.91 0.92 nm20 nGRC_ 0.05 0.90 0.88 0.87 0.88 nm22 nGRC_ 0.05 0.85 0.90 0.89 0.87 nm24 nGRC_ 0.05 0.81 0.83 0.91 0.86 nm25 nGRC_ 0.08 0.84 0.89 0.91 0.92 nm26 nGRC_ 0.11 0.76 0.81 0.95 0.96 nm28 nGRC_ 0.05 0.66 0.81 0.91 0.94 nm29 nGRC_ 0.06 0.89 0.90 0.88 0.92 nm30 nGRC_ 0.08 0.74 0.76 0.90 0.92 nm31 nGRC_ 0.07 0.76 0.83 0.91 0.92 nm32 nGRC_ 0.06 0.79 0.83 0.89 0.87 nm33 nGRC_ 0.24 0.83 0.86 0.84 0.85 nm34 nGRC_ 0.08 0.82 0.86 0.91 0.90 nm35 nGRC_ 0.10 0.86 0.86 0.92 0.84 nm36 nGRC_ 0.05 0.64 0.67 0.92 0.87 nm37 nGRC_ 0.07 0.87 0.86 0.88 0.88 nm38 nGRC_ 0.07 0.84 0.88 0.84 0.87 nm39 nGRC_ 0.06 0.81 0.83 0.85 0.89 nm40 nGRC_ 0.05 0.78 0.87 0.85 0.87 nm41 nGRC_ 0.07 0.67 0.69 0.89 0.89 nm42 nGRC_ 0.09 0.73 0.80 0.90 0.94 nm43 nGRC_ 0.11 0.67 0.76 0.94 0.94 nm44 nGRC_ 0.10 0.70 0.72 0.93 0.95 nm45 nGRC_ 0.07 0.61 0.65 0.91 0.90 nm46 nGRC_ 0.09 0.74 0.78 0.87 0.85 nm47 nGRC_ 0.09 0.70 0.81 0.87 0.88 nm48 nGRC_ 0.19 0.80 0.83 0.97 0.98 nm49 nGRC_ 0.08 0.58 0.62 0.91 0.84 nm50 CD4 + CD4 + CD4 + Th Th Marker- Th CD4 + CD4 + Central Effect. ID naive Th1 Th2 Mem. Mem. GRC_ 0.90 0.86 0.87 0.88 0.87 nm38 GRC_ 0.90 0.91 0.92 0.92 0.91 nm39 GRC_ 0.92 0.87 0.89 0.88 0.87 nm40 GRC_ 0.89 0.86 0.87 0.88 0.87 nm41 GRC_ 0.89 0.86 0.87 0.89 0.89 nm42 GRC_ 0.91 0.86 0.89 0.89 0.88 nm43 GRC_ 0.92 0.90 0.91 0.91 0.90 nm44 GRC_ 0.93 0.75 0.83 0.87 0.84 nm45 GRC_ 0.86 0.67 0.68 0.76 0.73 nm46 GRC_ 0.87 0.89 0.89 0.90 0.89 nm47 GRC_ 0.90 0.85 0.85 0.85 0.84 nm48 GRC_ 0.94 0.96 0.96 0.96 0.97 nm49 GRC_ 0.67 0.69 0.66 0.70 0.71 nm50 GRC_ 0.89 0.91 0.89 0.90 0.89 nm51 GRC_ 0.88 0.87 0.84 0.86 0.87 nm52 GRC_ 0.87 0.84 0.84 0.84 0.87 nm53 GRC_ 0.55 0.83 0.85 0.79 0.87 nm54 GRC_ 0.84 0.84 0.81 0.88 0.79 nm55 GRC_ 0.89 0.85 0.85 0.86 0.86 nm56 GRC_ 0.91 0.90 0.85 0.90 0.89 nm57 GRC_ 0.97 0.96 0.96 0.97 0.94 nm58 GRC_ 0.87 0.85 0.82 0.87 0.87 nm59 GRC_ 0.92 0.88 0.85 0.90 0.89 nm60 GRC_ 0.77 0.56 0.60 0.66 0.63 nm61 GRC_ 0.90 0.91 0.92 0.92 0.92 nm62 GRC_ 0.92 0.86 0.81 0.85 0.87 nm63 GRC_ 0.93 0.86 0.79 0.87 0.81 nm64 GRC_ 0.90 0.87 0.86 0.89 0.89 nm65 GRC_ 0.95 0.95 0.95 0.95 0.95 nm66 GRC_ 0.93 0.56 0.88 0.75 0.66 nm67 GRC_ 0.73 0.90 0.88 0.85 0.88 nm68 GRC_ 0.97 0.97 0.96 0.98 0.97 nm69 GRC_ 0.86 0.55 0.61 0.70 0.60 nm70 GRC_ 0.89 0.88 0.86 0.88 0.86 nm71 GRC_ 0.86 0.86 0.84 0.86 0.87 nm72 GRC_ 0.91 0.90 0.89 0.90 0.90 nm73 GRC_ 0.87 0.85 0.85 0.87 0.86 nm74 GRC_ 0.88 0.90 0.91 0.92 0.92 nm75 GRC_ 0.89 0.84 0.85 0.86 0.86 nm76 GRC_ 0.85 0.75 0.76 0.74 0.74 nm77 GRC_ 0.89 0.90 0.89 0.88 0.87 nm78 GRC_ 0.90 0.92 0.93 0.91 0.94 nm79 GRC_ 0.90 0.51 0.59 0.62 0.56 nm80 GRC_ 0.80 0.71 0.76 0.75 0.77 nm81 GRC_ 0.89 0.89 0.89 0.90 0.90 nm82 GRC_ 0.81 0.82 0.80 0.82 0.82 nm83 GRC_ 0.84 0.86 0.85 0.83 0.87 nm84 GRC_ 0.90 0.85 0.87 0.88 0.85 nm85 bGRC_ 0.91 0.91 0.91 0.90 0.91 nm1 bGRC_ 0.95 0.97 0.96 0.96 0.96 nm2 bGRC_ 0.96 0.96 0.97 0.97 0.97 nm3 bGRC_ 0.95 0.96 0.95 0.96 0.94 nm4 bGRC_ 0.96 0.96 0.96 0.95 0.96 nm5 bGRC_ 0.89 0.89 0.89 0.89 0.91 nm6 bGRC_ 0.90 0.86 0.87 0.88 0.87 nm7 bGRC_ 0.91 0.91 0.92 0.90 0.91 nm8 bGRC_ 0.89 0.76 0.78 0.81 0.80 nm9 bGRC_ 0.91 0.85 0.85 0.87 0.86 nm10 bGRC_ 0.92 0.92 0.93 0.92 0.93 nm11 bGRC_ 0.97 0.96 0.96 0.96 0.96 nm12 bGRC_ 0.93 0.94 0.93 0.93 0.91 nm13 bGRC_ 0.92 0.92 0.91 0.91 0.91 nm14 bGRC_ 0.92 0.93 0.95 0.95 0.94 nm15 bGRC_ 0.94 0.94 0.92 0.93 0.93 nm16 bGRC_ 0.92 0.92 0.93 0.92 0.93 nm17 bGRC_ 0.93 0.94 0.93 0.94 0.93 nm18 bGRC_ 0.91 0.89 0.88 0.91 0.87 nm19 bGRC_ 0.95 0.96 0.95 0.97 0.95 nm20 bGRC_ 0.92 0.92 0.92 0.93 0.93 nm21 bGRC_ 0.90 0.90 0.89 0.90 0.90 nm22 bGRC_ 0.91 0.89 0.88 0.90 0.91 nm23 bGRC_ 0.90 0.91 0.91 0.94 0.91 nm24 bGRC_ 0.89 0.87 0.89 0.89 0.87 nm25 bGRC_ 0.90 0.91 0.89 0.91 0.90 nm26 bGRC_ 0.91 0.86 0.87 0.88 0.89 nm27 bGRC_ 0.89 0.91 0.89 0.90 0.89 nm28 bGRC_ 0.94 0.94 0.94 0.94 0.94 nm29 bGRC_ 0.92 0.91 0.91 0.92 0.91 nm30 bGRC_ 0.95 0.94 0.93 0.94 0.96 nm31 bGRC_ 0.91 0.86 0.88 0.90 0.86 nm32 bGRC_ 0.90 0.89 0.90 0.92 0.93 nm33 bGRC_ 0.92 0.88 0.88 0.90 0.90 nm34 bGRC_ 0.90 0.85 0.84 0.88 0.85 nm35 bGRC_ 0.93 0.90 0.91 0.90 0.91 nm36 bGRC_ 0.92 0.88 0.88 0.90 0.88 nm37 bGRC_ 0.90 0.89 0.90 0.88 0.91 nm38 bGRC_ 0.91 0.90 0.86 0.90 0.90 nm39 bGRC_ 0.91 0.89 0.91 0.90 0.91 nm40 bGRC_ 0.92 0.89 0.87 0.91 0.91 nm41 bGRC_ 0.89 0.86 0.85 0.87 0.87 nm42 bGRC_ 0.90 0.88 0.91 0.91 0.90 nm43 bGRC_ 0.89 0.90 0.89 0.89 0.89 nm44 bGRC_ 0.93 0.91 0.93 0.93 0.94 nm45 bGRC_ 0.88 0.85 0.74 0.85 0.84 nm46 bGRC_ 0.91 0.82 0.83 0.86 0.85 nm47 bGRC_ 0.91 0.89 0.92 0.91 0.91 nm48 bGRC_ 0.91 0.91 0.91 0.91 0.92 nm49 bGRC_ 0.87 0.87 0.88 0.88 0.88 nm50 eGRC_ 0.97 0.97 0.96 0.97 0.97 nm2 eGRC_ 0.92 0.91 0.90 0.92 0.90 nm3 eGRC_ 0.61 0.94 0.92 0.88 0.96 nm4 eGRC_ 0.92 0.92 0.92 0.91 0.92 nm5 eGRC_ 0.91 0.90 0.88 0.89 0.90 nm6 eGRC_ 0.97 0.95 0.94 0.95 0.94 nm7 eGRC_ 0.93 0.92 0.91 0.93 0.93 nm8 eGRC_ 0.94 0.95 0.94 0.95 0.94 nm9 eGRC_ 0.91 0.87 0.85 0.87 0.87 nm10 eGRC_ 0.91 0.89 0.90 0.91 0.89 nm11 eGRC_ 0.89 0.84 0.88 0.89 0.87 nm12 eGRC_ 0.94 0.94 0.93 0.92 0.93 nm13 eGRC_ 0.89 0.85 0.86 0.87 0.86 nm14 eGRC_ 0.89 0.87 0.89 0.88 0.89 nm15 eGRC_ 0.93 0.87 0.86 0.89 0.89 nm16 eGRC_ 0.90 0.90 0.88 0.88 0.88 nm17 eGRC_ 0.89 0.85 0.86 0.87 0.87 nm18 eGRC_ 0.89 0.86 0.86 0.87 0.87 nm19 eGRC_ 0.87 0.85 0.83 0.87 0.85 nm20 eGRC_ 0.91 0.87 0.85 0.89 0.88 nm21 eGRC_ 0.91 0.91 0.92 0.92 0.93 nm22 eGRC_ 0.87 0.85 0.85 0.86 0.86 nm23 eGRC_ 0.84 0.82 0.81 0.81 0.81 nm24 eGRC_ 0.90 0.80 0.79 0.88 0.85 nm25 eGRC_ 0.86 0.78 0.81 0.82 0.78 nm26 eGRC_ 0.91 0.74 0.79 0.82 0.81 nm27 eGRC_ 0.88 0.78 0.75 0.77 0.77 nm28 eGRC_ 0.82 0.68 0.71 0.80 0.78 nm29 eGRC_ 0.64 0.72 0.70 0.73 0.78 nm30 eGRC_ 0.96 0.98 0.98 0.98 0.98 nm31 eGRC_ 0.98 0.99 0.99 0.99 0.99 nm32 eGRC_ 0.99 0.96 0.99 0.98 0.98 nm33 eGRC_ 0.91 0.92 0.92 0.91 0.91 nm34 eGRC_ 0.92 0.93 0.93 0.92 0.94 nm35 eGRC_ 0.90 0.87 0.85 0.87 0.86 nm36 eGRC_ 0.93 0.92 0.93 0.93 0.93 nm37 eGRC_ 0.92 0.93 0.93 0.93 0.93 nm38 eGRC_ 0.91 0.89 0.91 0.90 0.91 nm39 eGRC_ 0.90 0.84 0.89 0.84 0.86 nm40 eGRC_ 0.98 0.98 0.98 0.98 0.98 nm41 eGRC_ 0.90 0.87 0.88 0.90 0.89 nm42 eGRC_ 0.91 0.91 0.89 0.90 0.91 nm43 eGRC_ 0.91 0.91 0.92 0.92 0.89 nm44 eGRC_ 0.92 0.89 0.87 0.92 0.90 nm45 eGRC_ 0.93 0.90 0.92 0.92 0.91 nm46 eGRC_ 0.91 0.93 0.91 0.93 0.94 nm47 eGRC_ 0.90 0.89 0.90 0.89 0.90 nm48 eGRC_ 0.91 0.91 0.90 0.91 0.92 nm49 eGRC_ 0.91 0.90 0.90 0.91 0.91 nm50 eGRC_ 0.92 0.91 0.93 0.92 0.92 nm51 nGRC_ 0.96 0.98 0.98 0.97 0.97 nm1 nGRC_ 0.95 0.97 0.96 0.96 0.95 nm3 nGRC_ 0.96 0.92 0.96 0.96 0.92 nm4 GRC_18 0.91 0.91 0.93 0.94 0.92 nm nGRC_ 0.94 0.93 0.93 0.96 0.94 nm7 nGRC_ 0.91 0.89 0.90 0.90 0.89 nm8 nGRC_ 0.95 0.93 0.94 0.95 0.93 nm9 nGRC_ 0.96 0.98 0.97 0.97 0.97 nm10 nGRC_ 0.89 0.63 0.83 0.73 0.70 nm11 nGRC_ 0.93 0.95 0.93 0.91 0.89 nm12 nGRC_ 0.96 0.97 0.97 0.97 0.97 nm13 nGRC_ 0.89 0.85 0.86 0.85 0.86 nm15 nGRC_ 0.97 0.97 0.97 0.97 0.97 nm16 nGRC_ 0.96 0.95 0.96 0.96 0.95 nm17 nGRC_ 0.88 0.75 0.79 0.84 0.87 nm20 nGRC_ 0.90 0.85 0.88 0.89 0.84 nm22 nGRC_ 0.85 0.83 0.82 0.85 0.87 nm24 nGRC_ 0.87 0.89 0.89 0.88 0.92 nm25 nGRC_ 0.92 0.91 0.90 0.90 0.91 nm26 nGRC_ 0.93 0.96 0.95 0.96 0.95 nm28 nGRC_ 0.91 0.91 0.91 0.89 0.92 nm29 nGRC_ 0.92 0.81 0.83 0.86 0.86 nm30 nGRC_ 0.92 0.91 0.91 0.92 0.91 nm31 nGRC_ 0.92 0.92 0.90 0.92 0.93 nm32 nGRC_ 0.91 0.83 0.88 0.86 0.87 nm33 nGRC_ 0.86 0.84 0.85 0.86 0.84 nm34 nGRC_ 0.89 0.89 0.90 0.91 0.92 nm35 nGRC_ 0.90 0.91 0.91 0.92 0.91 nm36 nGRC_ 0.90 0.91 0.91 0.91 0.92 nm37 nGRC_ 0.89 0.83 0.81 0.86 0.84 nm38 nGRC_ 0.88 0.87 0.87 0.88 0.87 nm39 nGRC_ 0.90 0.88 0.89 0.89 0.88 nm40 nGRC_ 0.85 0.80 0.82 0.84 0.83 nm41 nGRC_ 0.90 0.90 0.89 0.90 0.88 nm42 nGRC_ 0.69 0.92 0.92 0.87 0.91 nm43 nGRC_ 0.95 0.90 0.92 0.92 0.94 nm44 nGRC_ 0.94 0.93 0.92 0.94 0.93 nm45 nGRC_ 0.90 0.88 0.88 0.88 0.87 nm46 nGRC_ 0.90 0.90 0.89 0.87 0.89 nm47 nGRC_ 0.88 0.87 0.89 0.87 0.88 nm48 nGRC_ 0.98 0.97 0.97 0.98 0.97 nm49 nGRC_ 0.89 0.90 0.92 0.90 0.89 nm50 CD8 + Cyto- Marker- toxic NK ID T-Cells T-Cells Discovery Fragment GRC_ 0.89 0.86 CGGCCTGGGCGTGGTC nm38 TTGCAAAATGCTTCCA AAGCCACCTTAGCCTG TT GRC_ 0.92 0.92 CCACAGACCCTTTCTC nm39 CTTCACTGATTACAGA ATCATACCAAGCACA GCG GRC_ 0.89 0.85 TGGGCCTGGTGCTTGG nm40 GTTTGCTAACTTCTGG TTCTTCATGTGTATCA CG GRC_ 0.89 0.84 CGACATGGGCAATGT nm41 GGGGAAAGAGACCAT TGTGTAAATGATCTAC AATG GRC_ 0.91 0.85 CGAAGGCCAGAGCCT nm42 GTTTGTAAACCATTAA CAGGAATAACAAGAG ATAA GRC_ 0.91 0.84 GACCGAGGCCGACAA nm43 TTCAGTCGCCACACAA GAGGTCAGAAATATA CTCG GRC_ 0.89 0.88 TGGGGATAAACGGTG nm44 TAACACTGGGGCAGG TCAGTTTCCTTGTTGG TACG GRC_ 0.85 0.73 TTTGAGGAAAATACCT nm45 TGAAACCGTCGGTAG GACTAGATAGGTGAC AACG GRC_ 0.78 0.70 CGTCTTGGTGATAACA nm46 GGCACTTGAGAAATA AGTTTTTAAAGAGTTG ATT GRC_ 0.88 0.90 AACACAGTGTGGGCT nm47 GATGCAATCAGTGTTT GCTGCCCTTGGGCGCT TCG GRC_ 0.87 0.82 CGGGCAGATTTTTTCA nm48 GAGCAATTGAATGTAT TCAAAGATGTCTTAAT TA GRC_ 0.96 0.95 GAAGCTGGGGCAGGT nm49 AACACGCAGAGCCGC CACGTGGAACGGTCT GTCCG GRC_ 0.65 0.61 GGAGGCACTTGTAGCT nm50 GAGTGAGGGCATTTCC TTTGTGCAGTGGTATG CG GRC_ 0.90 0.88 TTCTTGTTATCTCATTT nm51 AGGACTCATAACTCA GTTGTGTAAGCTTTAT CG GRC_ 0.88 0.87 ACTATCACTAGACATA nm52 TCCTCTCTTTAGAGAA ATCACACAAAATTCTA CG GRC_ 0.89 0.81 AAGGATTTGCTCTCCA nm53 GATGCAGCTGTGCCTT CCTTTGAAATATCTTT CG GRC_ 0.74 0.87 TCTTGAGAAATGTACT nm54 TTAGACTAGCTTGAGT TGACACATTACAAAGT CG GRC_ 0.83 0.85 CGGTATCAGCAATTGA nm55 AGCATTACAGTAAAA GACCTCCGATTACCAA CTG GRC_ 0.88 0.79 CGGCCCCTTCTGACCC nm56 CATAGCTGGCACGGG CTCCTGACCACAGGTA TGC GRC_ 0.89 0.90 TGCCCCGGTGGTGCAG nm57 TCAGTGGAAGCAGCT GTAATCTATGGGGTCA TCG GRC_ 0.98 0.96 CGGTGTCACAAGAAA nm58 ACCTTGCAGACTCGCC CTCGTAGACGGTCATG GAC GRC_ 0.79 0.77 CGTGGTACATGAGAA nm59 CCTTACTATAAAGTGG CTCTTTAGGACCGTTC TGA GRC_ 0.92 0.91 CATGAACTCTCTGCGT nm60 TCCAAACTATAGATTG TGATTAATTATTTTGT CG GRC_ 0.73 0.38 GCACCCCAGTTATCTA nm61 GCCCTCATCAATTTGT GCAAGAAGGCCGGGC TCG GRC_ 0.92 0.92 CGCAAGTGATTTATAG nm62 GCATTGTCTTTGCAGC CACTCTATGAGGCAG ACA GRC_ 0.89 0.88 CCACTCTGACCTTAGA nm63 CAAGTTACTTAATTGT CTCAGTGCCTTGGTTT CG GRC_ 0.90 0.87 ATTTCATCAACTGTCC nm64 CACTAACATCCTGTAT ATACCAAGCTTCTTAT CG GRC_ 0.91 0.87 CGCTTTGGAAGAAGG nm65 ATTAGGTAATTGTAGT ACAATCTTCCACCCAG TTC GRC_ 0.96 0.93 CGGACCTCAAGTCCCT nm66 GTGCTAGCCACGGTA GTTCTTCACACCCCGT CAC GRC_ 0.82 0.61 ATGGCGGATATGTATG nm67 CAACGCGTGTGGCCTC TACCAGAAGCTTCACT CG GRC_ 0.89 0.91 AGGTAGCCATGCTGCT nm68 AAGGTCACAGTCACT AAGATATTTTTTGTCA TCG GRC_ 0.97 0.97 GGTTACGGGGCAGTG nm69 GCCATGAGCCTCTGTC GGACTGACGCAAGGA GCCG GRC_ 0.70 0.34 AAAAAATAGACAACC nm70 TCCCAGTTGCCACAGA CATGTACTGTAAGCAG ACG GRC_ 0.91 0.87 CGGGAAATACACATT nm71 ATGCTAATGTTGATGA CAGAATTTATTTGGTT GCC GRC_ 0.88 0.80 CGGTGCCATCTTGTGA nm72 AAAGGGCTCTGCAGC TTTTAATGTGTACAGT TTC GRC_ 0.91 0.88 GGCCTACATTCTGTAC nm73 TTTGTGCTGAAGGAGT TCTGCATCATCTGCAT CG GRC_ 0.88 0.86 CGTGACGATGCAGAT nm74 GATGCAGAACTCCTTC AGCACAAAGTACAGA ATGT GRC_ 0.92 0.89 CGCCAGCCTGCATTTT nm75 AGATGGACCATAACT CAAGATAGGCGTTGA AGCA GRC_ 0.86 0.79 CGAGGGCACTGGACA nm76 TGCTGGATTTGGGGAG ACTGTTATGCGATCTC AAA GRC_ 0.77 0.58 CAGAGGAAGCCACAT nm77 AACCTCAAAAGGTCA AGACACCTAGACATG GTCCG GRC_ 0.89 0.86 CAACCTGTCCACTCGG nm78 TTTTCTGTTTCTTTGAG ATTATTTTCTACTAAC G GRC_ 0.93 0.93 CGGTGTGATGTGATGA nm79 AATCAGGATTTTGTGT AAGCTAGCTCTCAAG AAA GRC_ 0.80 0.47 ATCCTGCTTCCATGGA nm80 GTAAAATTCCAGACTG GGACAAGCGTTCTTTC CG GRC_ 0.82 0.68 CGTGTCTCTTTAAAGC nm81 TGCTATGTGAACAGCT TTTACAGTCATTAAAT TT GRC_ 0.90 0.87 TGTATGTCCAGCTGGA nm82 CTTGGCAGAAGTACA CAGACTGGTCCTCCTT CCG GRC_ 0.85 0.80 GACACATGATCCTCGG nm83 GCTGCTGCTGGGCTTT AGCTACCCAGAGATT ACG GRC_ 0.87 0.86 ATTTCCTATGGCCAGT nm84 GTTTACAGAAGTAA GACTGTGCAAACTTTA TCG GRC_ 0.90 0.88 GGCTTCTGACTGGAGG nm85 ACAATGACCCAGCTG ATCCTTCTGACGTCTT ACG bGRC_ 0.91 0.89 AAGAAAGAACCCTTT nm1 AAATAAAGGGCCCAC ACTGGCTGCCAGGGA GTGCG bGRC_ 0.94 0.95 CGGGGGGCCACCGAA nm2 TACTCCCCGAGCGCAT ACTATTTACAGAAGA GTCA bGRC_ 0.97 0.97 GACGTGCAGATAACG nm3 TTGAGCTGCCCTGTCC CCGAGCCATAAGCAG ACTCG bGRC_ 0.95 0.96 CGGTCACTTCCAGGTT nm4 TTGACGATCATGAATA ACGTTTCTGTCGACAT CT bGRC_ 0.96 0.96 CGCCTATCGGCCCATC nm5 TCCCTGCTGTCCATCA GGCCGGGCCCCCGCCT CA bGRC_ 0.91 0.90 CGTCCTAGACACCCTG nm6 GCCTGGAAACTAGGA CATCTGCCTCGGGCCT GTT bGRC_ 0.88 0.85 CGCTGCAGCAGATGG nm7 TCTTGGAAATACAACA GGCTGCATTCTAACTG CTG bGRC_ 0.92 0.92 ATAACTTGGAGGCAG nm8 CGTAGATGGCGCCTG GTGACTGCAGTGTGCC CACG bGRC_ 0.84 0.71 CGTCAGGGCTGTGGTG nm9 ATGAAGTCCAGATGTT ATAACTTAACAGTGTT TT bGRC_ 0.88 0.82 GGCCTGCTGTCCCACT nm10 GCCATGCTCATCTGCA TATGTATGGTTTCATT CG bGRC_ 0.93 0.93 CGCTAATGCCAAGAT nm11 AAGCTAATGCTGTGCT TCACCTGGACACAGG GAAA bGRC_ 0.97 0.96 TCACCTGCGGACTGAC nm12 CCCGTGCTGGGGAGG TGGTGGCTGGTAGTGA GACG bGRC_ 0.94 0.94 CGAAGGCTTTGTAATT nm13 CACAGTGATAAGTGC AGTTAATATGTTATCT GAT bGRC_ 0.92 0.93 ACTGCCCATTTTTTAA nm14 AACTTCAAATCCAAA AGATGTGATAAATAG TACG bGRC_ 0.92 0.93 CTCTCGGGAAGACAG nm15 GGCTGCTGTGTATCCT GATTGTGGTGGTGGAT ACG bGRC_ 0.95 0.91 GAGGGGACAGTCCTG nm16 GGTCCCCGCCAATCCG GCCCTTGAGGTTGAGC TCG bGRC_ 0.90 0.93 ATAGGTGAATTCTATA nm17 GCCAGGTGGCCTCCA GAAGCTFACGAAATG ATCG bGRC_ 0.93 0.93 CGCCCTGCGTTGCGTT nm18 CTCCACACAGCAGCC ACGGTGACTTTGTTAA AAT bGRC_ 0.90 0.88 CGGAATATTCAAAAC nm19 CAGATGGACAGTTAG GTCGATAGATAAGAC AGATA bGRC_ 0.94 0.94 AGTGCGCTGCTGCGG nm20 GAGGAAGCCAGTGTC TTCCTGGAGACGGCTT CACG bGRC_ 0.93 0.90 CGCTTTGAGATTGAAG nm21 AGAACATACACTGGA CCATATAGGGGTCTTC TAC bGRC_ 0.91 0.87 CGGCTTCCTTTGATGG nm22 GAGACAGGAGGAGTA GAAATAAGCTGAGCT ACAC bGRC_ 0.90 0.91 ACTGAGCAGCAAGTA nm23 TTCCTTGTGTACCAGT CTCTGTTCCAGAAACA ACG bGRC_ 0.93 0.91 CGGAGAAATGCAAAT nm24 CTGATAATAAGCACAT ATATAGATGGCATTTA AAT bGRC_ 0.86 0.89 GCTTTATCTAACAATT nm25 TATTTAACAAACAGTT AACTAGCACTGTGTGC CG bGRC_ 0.92 0.90 CGGAACCCTGACTTTG nm26 GAGGCTTCAGACATCC TGAAATATAATTCAGA TA bGRC_ 0.91 0.89 CCTGGTCACAACATTC nm27 AGAGGACACACAGGT AGGATTAACAGTAAA ATCG bGRC_ 0.92 0.87 GCCAGGATCACAAAG nm28 TTTCTGCCTTATCATTT ATGGTTATTGTTACCT CG bGRC_ 0.94 0.95 AATAAGAAGAGTCCG nm29 TACCTCTTTCCCCTCA CTCTGCACCCAGAATA CCG bGRC_ 0.91 0.89 TTCAGCAGATGAGATC nm30 TCAGCAATCCCCACTA GGCTGGCTTCTAATAA CG bGRC_ 0.96 0.95 TGGCTTCTGCCAGAGA nm31 AGCCCCGGACAGCTG CGAGCGCTGGCTGAG AACG  bGRC_ 0.90 0.82 GGCAGGTCTTCTGACT nm32 TGGTCTCATTTTCTGC ATGGCTTTCTCCCTCT CG bGRC_ 0.90 0.91 CGTGGCTTTTGATTAT nm33 CTGCAAAGATTAATG AGCCCTAATGAACGG GTCA bGRC_ 0.92 0.90 GTCCCACTGGGGCAC nm34 ACAGCAGAGCAATGA AATTCCTGCATATTAA GACG bGRC_ 0.83 0.84 CGGTAGACTGATGAA nm35 ATAAGGTTTGGTTCAT ATCCATAACAGTTGAC TAC bGRC_ 0.89 0.87 CGGTAGGTGTGCACA nm36 AGCCAGAGCAGAGTC CCATTCCTTGCATCCG CCAC bGRC_ 0.84 0.83 CCTGGCACCTGCTTCA nm37 CAGCCTTCCCGCTTGC CTGCTTTGTGGTGAGT CG bGRC_ 0.91 0.89 CGGTCTGATCTGAACT nm38 CGGCTTCAGTTGGTCT GGAATGCACCGGCTG CAT bGRC_ 0.91 0.91 CGCTGAATCATGGAGT nm39 TTATCTTAAGGATGGA TCTGAATGAGATCTGA TA bGRC_ 0.91 0.87 AAATTCTGAATTTTCG nm40 CTACACTGTCCACAGT ACCAAATGGCAATAA CCG bGRC_ 0.93 0.91 CGGTGGCTGTTTCCAT nm41 AGTAGCCTCATATCAC TGCCAAATCTCATCTG AT bGRC_ 0.86 0.88 CTATCTGTGACAGATA nm42 ACCTATATCACAGATA GATCTATCTGTGACCT CG bGRC_ 0.89 0.88 CGCAATAAGCACAGA nm43 GCTGGACTTGAACCCA AGTTTTGCCACACAGG CCT bGRC_ 0.90 0.90 GGCTCTGTGGGTTTGG nm44 CTCTTAGAGTCAAGAT GGTCACCGCCTCCAAG CG bGRC_ 0.94 0.93 CACTAATTACCACTCA nm45 GTTCTTGGGCTGTAGC AAAGATAATTTCAATT CG bGRC_ 0.89 0.86 CGCAGTTATCTGTGGC nm46 TGATCATGGCTTGTCA TACTGCTACTCCTAGA TG bGRC_ 0.89 0.85 CGCTGGTGTGGGACC nm47 AGTCTCCTAGACCCAA GTGCTAGGAGTAGAA TGCT bGRC_ 0.89 0.86 GCATCCTAACAAATG nm48 AACAATCTTTAGCTAA AGACACTGACCAGAT TACG bGRC_ 0.91 0.89 CGTATGAGGTTATGTA nm49 GCATGTGAGGATAGG CATAGCTTTGTTACGT GTC bGRC_ 0.90 0.91 CGCTGATAAATCTCTT nm50 GAGTTTTTCAAGAAGG TGACAGTGTATACCAT GA eGRC_ 0.97 0.98 CGCGGTGACACCTAC nm2 AGCCACGCAAGCACC TGCGTAAACACGTGCT ACAG eGRC_ 0.92 0.86 CGGCAACCCCAAAGC nm3 ACCTGTTAAGACTCCT GACCCCCAAGTGGCA TGCA eGRC_ 0.72 0.98 CCATGGAGGAGCGTG nm4 ACGGAGAGATCTGCG TGTGACGCTGTGTGCT CTCG eGRC_ 0.92 0.93 CCCTATAATATCTTTA nm5 CTGTAAGGCAGCTACT TCTCCCTAAATAATTT CG eGRC_ 0.88 0.90 TAAAAAATTTCTTGCC nm6 ACATACGAGTTTAAAC CAAGATAATCACGGC ACG eGRC_ 0.96 0.95 CGCTATAGCAGTTTTT nm7 AAAAGCTTCTTCGATT GTTGACCGGTCCGTTA AG eGRC_ 0.93 0.93 CGGAAGCCAAGCTCT nm8 GTCCCAAGCACTGTGC TGATGATATCTCATTT CAT eGRC_ 0.95 0.96 CGCCGCTGCACCTCAT nm9 CCTCCATGCTGTCCAC CTGCCAGGATAAGGA GTG eGRC_ 0.88 0.87 CGTGGAAGAGGGACA nm10 GAATTTTAGAGAGAG AAACTCATTTGAGAA ATGGG eGRC_ 0.91 0.89 CGTCGTTATTCTTAGG nm11 AGATGCATGTTGAAAT ATTTAGAAATGATTTT AT eGRC_ 0.88 0.84 ACAGGGACCTAATTA nm12 ACTGACAGTTGGTCTG ATTGCCAAGCTGAGG GGCG eGRC_ 0.93 0.93 CGAAACACAGTCATTC nm13 ATGTTGGTAATTGTGA CAGAGATTATGTGGCC CA eGRC_ 0.85 0.82 AGATGGATAGTGGCTT nm14 CCTAATATCCCCTTTT CATCAGTGTTAAAAAT CG eGRC_ 0.89 0.88 TGAGGTTAAGAAATTT nm15 GCTCATGGCCATACAC GCAGCAAGCAGTTCT ACG eGRC_ 0.91 0.87 CGGTTGCTTAAGCTGA nm16 CACTGCAGAGCATTGC AAGAAGTGTTGATTA AAA eGRC_ 0.90 0.91 ATTTGTATTTTGACAG nm17 CCCATGGTAGCATCAG ATAAATTGCCTTTTAA CG eGRC_ 0.88 0.85 CGCACAACTGCTCCAT nm18 CTTTTAAGATATTGGA AGTGAGAGCACGGGA GGA eGRC_ 0.88 0.87 CTCCACAATAAGCTAA nm19 AGCCAACTCCTGCAAC AGGCTCCTGTGATCAA CG eGRC_ 0.87 0.81 CGGTGCCTGGGGCTCA nm20 GGTCTGTTCAAACTCC TGCTCACAGAAGCCTA CA eGRC_ 0.88 0.85 CGCAATCCTCAGAAG nm21 CTGACAGGAGCTTCA GAGAGGAGAATTACC TTACC eGRC_ 0.93 0.91 ATTTACACATCCATAG nm22 GCCTCATTTCTGCTGT TCTAAAGAGTCTTTAT CG eGRC_ 0.86 0.84 AACTCCTAAGGCCAA nm23 AGGAATGTGGTATGCT CACTGACTTGGCTTGG ACG eGRC_ 0.83 0.79 GGGGTAAATGGATGC nm24 AGAGCAGGCTTCTAA GGTGCAGTCCCCCTCC TTCG eGRC_ 0.84 0.77 CCAGGTGCAACATAT nm25 GCATGCCAGTTGGTGC ATGCAGCTTGTGAGGT CCG eGRC_ 0.83 0.78 CGGGCAGTCTGTGGTT nm26 CCTGACCAGACTGCTG GGGGTCAAATCTCTTT CA eGRC_ 0.82 0.75 GAATTTCCTAATATAT nm27 TTCTAACAGATAATGG TCACCACCACTACCCT CG eGRC_ 0.81 0.67 CGATTGTTAGGAAACC nm28 AAATGTTCTGAACATT ATTTTCATTAGAAAAG GG eGRC_ 0.81 0.66 AGCGGGAGGCTGGTG nm29 GCGTGCATCAGGCCAT GGGGGTGGGGCTTGG ACCG eGRC_ 0.68 0.77 CGACTGCTCAAACTGG nm30 GTTTGGAGAACAACC CAGTATGGCTTTTACA GAG eGRC_ 0.98. 0.98 CGGGATAAAGCACAG nm31 CTCCTCCGCCAGCCCG GCGCGCAGCGGGCCT CACC eGRC_ 0.99 0.98 CGCACTCCGGTGACTC nm32 AGAATTGTCGCCGCTC CGTGCAAGTAAGTGTT TG eGRC_ 0.99 0.96 GGTGATGAACGAGAA nm33 TGAGCGCTATGACGC AGTCCAGCACTGCCGC TACG eGRC_ 0.91 0.93 AGTATCTAGAAAAAC nm3434 CCAGAGAATGATATTC CACAAAACGGTAAGC ATCG eGRC_ 0.95 0.92 CGCGGGAGCTGCGGG nm35 CTGCGGTGATCCAGCT TCTGGACACCTCCTAT CTG eGRC_ 0.89 0.84 CGCCCTAGGGCCAAG nm36 AGTTGGGCCCCGTCTG AGCTTTTTTCAACTCT GTT eGRC_ 0.93 0.92 CCCAATAGAGGCTGTC nm37 TCAACAGTGGCCAAC AGAACTCTCATGAGTA TCG eGRC_ 0.94 0.95 GTAGACCTTGCTAATA nm38 ACTTGCCTATAAGTTC CACAATACTCCCACTA CG eGRC_ 0.91 0.89 CGCAGAGTCTTGACCA nm39 CAAGGAAAATCTTGTT TTTGAGCAATAACCCT TC eGRC_ 0.85 0.80 CGTCAAGCTTTGTTGA nm40 GTCAGACAGTGTCTGT CCAAACTACTCAAGTC AG eGRC_ 0.98 0.98 GGGCGAAGTCGCTGG nm41 TGCCAGAGTCAATGA CACGGAGAGGAAACG CTTCG eGRC_ 0.90 0.89 TTTACTGATTTAGGAT nm42 GTCGACCATCTAGTCT GCCAGAGCTGCAATA ACG eGRC_ 0.89 0.91 CGGCAAGTCCTATTGA nm43 GATTATAACAATGAC ACTGATAAAAAAGAA GATG eGRC_ 0.92 0.93 AGCACGTTCATGACCC nm44 TTGAAAGTCTTCGAAA ACAGATTACTGGGCTT CG eGRC_ 0.89 0.87 CGTGCACTCTGAACAA nm45 GCATTCATTTGGCTGC ACAGGGCCAGATCAA GGT eGRC_ 0.91 0.88 ACTAGCTTTGCGAAAG nm46 CCACAGGGAAGTGAT CTTGGTTGTGCAGGTG TCG eGRC_ 0.93 0.94 AAATGAATGTAGATA nm47 CCATCTTAGCCAGGTG ATGAAACAAACTGGT ATCG eGRC_ 0.90 0.88 CGGAAATCAGAGGGA nm48 GAAGACGCATATCTTG TTTCAGTGAGGGTGAT CCC eGRC_ 0.91 0.91 CGGTCAGAGGGGACC nm49 ATCTGTTTATCTTACA GGCTTAATATGATCAC AGG eGRC_ 0.88 0.88 TACCAGCCCTTCATTT nm50 CTTTGCTTTGACTCTTT AATTTCCAAGATAATC G eGRC_ 0.93 0.92 CGGAAGGCTGGGGAA nm51 ACAGGCTCTGCCCTAT ATCTGAGGGAAGTGT GCAT nGRC_ 0.97 0.96 CGCCAGGTTTCGAGAT nm1 GAAATCTCCGCCCTGT AGCTCCGGACGTCCTC CA nGRC_ 0.97 0.97 CGGCTAAGTCCCCACG nm3 TACGCCATTAAACAAC GGTCAAATGGTAACA TGT nGRC_ 0.96 0.95 CTGCCCTTGGTCAGCA nm4 CCGTGTAGGGCATGTG CTCACCCGCTGGAGAT CG GRC_18 0.93 0.94 CGAAACAGATTGCATT nm TCCTAGAAGGCCCCCA GCGATGTGGATTGAA GCG nGRC_ 0.94 0.93 CGGCTTGAGCGCCAG nm7 CAGCCTGCACAGGTTC CATGAGCTGGAGAGC TGCG nGRC_ 0.92 0.91 CGGACTACGAGTACC nm8 AGCACTCCAATTTGTA TGCCATATCAGGTATG TGG nGRC_ 0.95 0.88 AATACCTGGCACGCC nm9 AGGGTGATGCAACTG GGAGCTTCTGCACGTT CGCG nGRC_ 0.98 0.98 CAGCGCCCGTGTGATG nm10 ATGATGCTCACGCTCC GGTGTGACACAGACG GCG nGRC_ 0.75 0.48 CGGGAGGAGCTGGGT nm11 GGATACCTTTCTAACT TCCGAGGCTGGCTACT CCT nGRC_ 0.93 0.94 CCCTCTGCCCAGCGCG nm12 TCTGGGACGTGTGCCC AAGAGCTTATTGAGA ACG nGRC_ 0.96 0.95 TCAGGAAATTGCGAA nm13 GAAATTCTGCGGCGG GTGCAGGATGCCCAC CCTCG nGRC_ 0.92 0.86 CGTGGAGATGAACTA nm15 GAACAGGTATGAGGT TCTAGCAGAAGAAAC ATTTG nGRC_ 0.97 0.97 CGATATTAGAAAGGA nm16 GCTCAAGGTAGTACA CTTCACGTGCCCCGGT AACG nGRC_ 0.88 0.92 CGGCACTTTCAACCAA nm17 ACAGAGACACTCCGG CTCGTACACAACCAGC CGT nGRC_ 0.91 0.90 CGCAATCCAGTCACAC nm20 TTGTGAAAATGCTGAA GACGGTGGTTACGGA AGC nGRC_ 0.89 0.88 CGCTGAGCCAGAACA nm22 ATAGGACTTCTTCTGT AGTTGTGAAACTTGTC AGT nGRC_ 0.86 0.83 GTACCAACTGAATTCA nm24 ATTTAAAAACAAAGA TGTCAGACATGCATCT TCG nGRC_ 0.90 0.89 GTGTATGGATTCGGCA nm25 TGGAGCCCTCAGCTGG CGGCTCTGGGTGCTGA CG nGRC_ 0.92 0.86 CGCACTTCTGTGCGCT nm26 CACTATGAGAAGCTGT GTTTACTCGCTCCGTG CT nGRC_ 0.96 0.94 TCCCAGTCATTCTCGG nm28 GGTAAGTTCCGAAGTT GGAGGTGTCGCCTTCG CG nGRC_ 0.95 0.91 CGTCCTCCGTCTGCCG nm29 CCCACTAATCGTTCCC CATACAGACTTCCTGG CG nGRC_ 0.90 0.77 AGGTCACAGATGCAG nm30 ACGTTTGCTCGAAGTG GCTGCCGAGCTCAGA CCCG nGRC_ 0.90 0.92 GTGGAGGATCCAATTC nm31 TAAGACAGCTCATTCA TTCACATGGCTGTTAG CG nGRC_ 0.92 0.91 TTCTCAACACCAGTTT nm32 TCTGAGCAGGGTGAA TAACTCTGCTCATACC TCG nGRC_ 0.87 0.78 TCCTATTACTCCAGAC nm33 GAATCTGTTTCATGTG CTGAAGCTCTCCCCTT CG nGRC_ 0.84 0.84 AAAACCAAGTCTAGG nm34 ATTTTTCCATGGATGG TTTCTCAGCCGCTCTC ACG nGRC_ 0.92 0.90 GGCTGTGGTTCTCTGC nm35 TTGTGCCCACTTTGTG TTTGTAAATAGCGAGT CG nGRC_ 0.91 0.91 CGGGGGCTAGAGTTC nm36 ATAATTTCTGGTAATC GCTCAACCCTGTGATT ACG nGRC_ 0.92 0.91 CGCTTTGCTTAGAGAT nm37 CAACAGAGTGACATC CTAGGGTCTGAGCCTC AAC nGRC_ 0.83 0.83 CAAAAGCCTGTGAGG nm38 AGCTCCTGGAAGACA TTAAGTTCTCTACAGC AACG nGRC_ 0.87 0.78 CGCAGGAGTAAAATT nm39 GGGTAAAACAAGCAC ATGGGAACTGAGGCA ATCTC nGRC_ 0.87 0.83 CGGGTGCAACTGGCA nm40 CCAAGAACAACACCC ATGCCCAGGTGACAA CTGCG nGRC_ 0.82 0.69 CGTGTTCATAAATGAG nm41 TGCAGTGATATCAATT TAAGAACATCCATCAT GT nGRC_ 0.88 0.88 ATGTTTGTACACAGCT nm42 GCCTCCTTGACTGTAG TTGATTGGCCTCTGTG CG nGRC_ 0.88 0.95 GAGACGAGCGTCTCA nm43 GACTTGAGGAAATAC ACGCGTGGAAGACGT GCGCG nGRC_ 0.94 0.92 GTTCTTCTCCGTGACA nm44 GGATGTTCTTTTCCGT GACAGGAAGTTCCGT CCG nGRC_ 0.94 0.91 AAGTGGGATCCGCAA nm45 GATGATGGATGAGTTT GAGGTAGACCCCTTTC CCG nGRC_ 0.91 0.84 TGACGCTGTATTTCCT nm46 GAAACTGCTCAGCAA GATTTCCAGCTATCCA GCG nGRC_ 0.87 0.90 CGGTCAGTTCCTGTGA nm47 GGAGGAAACAATGAT ACTGCATTATAGACAT CGT nGRC_ 0.86 0.86 CGGGGAGGGACTAGA nm48 TCAGAAGAGATCAAG GGCTCTATTCAGGAAC GTTG nGRC_ 0.98 0.97 CGTGGGCATCACGTA nm49 AGCAGCACACTAGGA GGCCCAGGCGCAGGC AAAGA nGRC_ 0.89 0.90 CAAATCACTGTAGTTC nm50 AGACAAAACCTTCAT ACCATMATTATTTA ACG

TABLE 4H T-Cell Marker Basophil Marker- Target- Granu- ID ID SYMBOL Accession locytes OTL_ cg0338 CCDC57 NM_ 0.95 nm18 8043 198082 OTL_ cg1916 HDAC5 NM_ 0.97 nm19 3395 001015053 OTL_ cg2461 CD3E NM_ 0.92 nm5 2198 000733 OTL_ cg0754 CD3G NM_ 0.90 nm4 5925 000073 OTL_ cg2444 TMEM177 NM_ 0.86 nm22 1810 001105198 OTL_ cg1731 — — 0.93 nm23 1865 OTL_ cg1761 HLA-E NM_ 0.90 nm24 5629 005516 OTL_ cg0865 1L32 NM_ 0.89 nm25 9421 001012632 OTL_ cg0793 — — 0.89 nm26 0673 OTL_ cg1011 CDR2 NM_ 0.82 nm27 1816 001802 OTL_ cg2564 CD3D NM_ 0.88 nm28 3644 000732 OTL_ cg0763 MPI NM_ 0.87 nm29 0255 002435 OTL_ cg1822 — — 0.92 nm30 2759 OTL_ cg0277 TRIM15 NM_ 0.89 nm31 2121 033229 OTL_ cg0327 — — 0.87 nm32 4669 OTL_ cg2527 TNRC6B NM_ 0.76 nm33 6892 001024843 OTL_ cg0923 — — 0.88 nm34 2358 OTL_ cg2421 TNIP3 NM_ 0.82 nm35 5459 001128843 OTL_ cg2613 — — 0.88 nm36 7915 OTL_ cg0440 ATP1A1 NM_ 0.86 nm37 3423 001160233 OTL_ cg2056 — — 0.81 nm38 7280 OTL_ cg2711 UBASH3A NM_ 0.65 nm39 1890 001001895 OTL_ cg1050 CCDC57 NM_ 0.82 nm40 5658 198082 OTL_ cg2496  PLCG1 NM_ 0.86 nm41 1795 002660 OTL_ cg0002 CD2 NM_ 0.79 nm42 7570 001767 OTL_ cg2331 — — 0.81 nm43 8020 OTL_ cg1484 ACSL6 NM_ 0.80 nm44 1483 001009185 OTL_ cg0300 HACE1 NM_ 0.85 nm45 2526 020771 OTL_ cg1792 SEPT9 NM_ 0.84 nm46 2695 001113492 OTL_ cg0304 — — 0.63 nm47 0292 OTL_ cg1175 BCL11B NM_ 0.71 nm48 3157 022898 OTL_ cg0720 — — 0.81 nm49 3767 OTL_ cg1522 CHD3 NM_ 0.70 nm50 7911 001005271 OTL_ cg0183 — — 0.77 nm51 0053 OTL_ cg2627 — — 0.79 nm52 1776 OTL_ cg1623 HMHA1 NM_ 0.84 nm53 9536 012292 OTL_ cg0844 FAM71B NM_ 0.79 nm54 5740 130899 OTL_ cg2766 SECTM1 NM_ 0.70 nm55 6046 003004 OTL_ cg2605 — — 0.81 nm56 3876 OTL_ cg0611 RPS3A NM_ 0.79 nm57 0802 001006 OTL_ cg0755 OR5AU1 NM_ 0.72 nm58 5731 001004731 OTL_ cg1382 SET NM_ 0.62 nm59 7677 003011 OTL_ cg2403 CACNA1C NM_ 0.66 nm60 3471 001129844 Eosino- Neutro- Non- phil phil Classical classical Marker- Granu- Granu- Mono- Mono- ID locytes locytes cytes cytes OTL_ 0.96 0.97 0.96 0.96 nm18 OTL_ 0.95 0.97 0.92 0.91 nm19 OTL_ 0.95 0.93 0.94 0.93 nm5 OTL_ 0.89 0.90 0.92 0.89 nm4 OTL_ 0.89 0.92 0.91 0.92 nm22 OTL_ 0.93 0.91 0.91 0.89 nm23 OTL_ 0.88 0.93 0.94 0.92 nm24 OTL_ 0.90 0.91 0.90 0.90 nm25 OTL_ 0.88 0.88 0.89 0.90 nm26 OTL_ 0.75 0.84 0.85 0.86 nm27 OTL_ 0.89 0.89 0.91 0.88 nm28 OTL_ 0.89 0.89 0.89 0.87 nm29 OTL_ 0.90 0.92 0.90 0.94 nm30 OTL_ 0.85 0.84 0.87 0.85 nm31 OTL_ 0.87 0.86 0.85 0.89 nm32 OTL_ 0.58 0.87 0.89 0.91 nm33 OTL_ 0.89 0.89 0.85 0.86 nm34 OTL_ 0.84 0.87 0.88 0.86 nm35 OTL_ 0.89 0.89 0.88 0.87 nm36 OTL_ 0.89 0.89 0.90 0.89 nm37 OTL_ 0.84 0.85 0.83 0.81 nm38 OTL_ 0.86 0.89 0.89 0.88 nm39 OTL_ 0.73 0.81 0.86 0.82 nm40 OTL_ 0.86 0.85 0.84 0.82 nm41 OTL_ 0.84 0.86 0.88 0.84 nm42 OTL_ 0.85 0.85 0.86 0.85 nm43 OTL_ 0.79 0.77 0.82 0.84 nm44 OTL_ 0.86 0.89 0.85 0.85 nm45 OTL_ 0.71 0.73 0.87 0.68 nm46 OTL_ 0.84 0.90 0.89 0.87 nm47 OTL_ 0.76 0.80 0.79 0.75 nm48 OTL_ 0.84 0.85 0.86 0.83 nm49 OTL_ 0.72 0.82 0.77 0.72 nm50 OTL_ 0.61 0.71 0.78 0.79 nm51 OTL_ 0.83 0.81 0.81 0.77 nm52 OTL_ 0.82 0.83 0.82 0.81 nm53 OTL_ 0.84 0.85 0.84 0.81 nm54 OTL_ 0.73 0.73 0.76 0.72 nm55 OTL_ 0.83 0.79 0.77 0.72 nm56 OTL_ 0.77 0.85 0.82 0.83 nm57 OTL_ 0.69 0.72 0.69 0.69 nm58 OTL_ 0.56 0.72 0.80 0.74 nm59 OTL_ 0.68 0.71 0.71 0.66 nm60 NK Marker- clas- B- CD4 + CD4 + ID sical Cells Th naive Th1 OTL_ 0.84 0.97 0.07 0.02 nm18 OTL_ 0.94 0.86 0.18 0.02 nm19 OTL_ 0.89 0.94 0.14 0.04 nm5 OTL_ 0.87 0.88 0.08 0.04 nm4 OTL_ 0.90 0.82 0.07 0.05 nm22 OTL_ 0.89 0.82 0.18 0.00 nm23 OTL_ 0.74 0.77 0.08 0.04 nm24 OTL_ 0.80 0.83 0.16 0.06 nm25 OTL_ 0.79 0.89 0.09 0.09 nm26 OTL_ 0.84 0.83 0.08 0.04 nm27 OTL_ 0.57 0.90 0.10 0.06 nm28 OTL_ 0.77 0.82 0.08 0.07 nm29 OTL_ 0.90 0.81 0.19 0.11 nm30 OTL_ 0.74 0.83 0.10 0.05 nm31 OTL_ 0.61 0.91 0.09 0.05 nm32 OTL_ 0.85 0.73 0.03 0.03 nm33 OTL_ 0.85 0.89 0.22 0.10 nm34 OTL_ 0.55 0.63 0.09 0.04 nm35 OTL_ 0.57 0.86 0.12 0.11 nm36 OTL_ 0.81 0.64 0.08 0.13 nm37 OTL_ 0.76 0.79 0.11 0.06 nm38 OTL_ 0.84 0.92 0.14 0.13 nm39 OTL_ 0.58 0.83 0.11 0.05 nm40 OTL_ 0.83 0.77 0.16 0.09 nm41 OTL_ 0.81 0.82 0.17 0.10 nm42 OTL_ 0.51 0.83 0.11 0.08 nm43 OTL_ 0.78 0.84 0.11 0.07 nm44 OTL_ 0.78 0.81 0.18 0.16 nm45 OTL_ 0.68 0.68 0.08 0.03 nm46 OTL_ 0.59 0.63 0.09 0.07 nm47 OTL_ 0.87 0.70 0.08 0.08 nm48 OTL_ 0.66 0.84 0.15 0.12 nm49 OTL_ 0.78 0.82 0.06 0.05 nm50 OTL_ 0.73 0.72 0.04 0.02 nm51 OTL_ 0.79 0.71 0.22 0.11 nm52 OTL_ 0.58 0.74 0.14 0.09 nm53 OTL_ 0.56 0.64 0.11 0.12 nm54 OTL_ 0.57 0.60 0.14 0.03 nm55 OTL_ 0.68 0.75 0.19 0.08 nm56 OTL_ 0.83 0.66 0.18 0.21 nm57 OTL_ 0.61 0.55 0.16 0.09 nm58 OTL_ 0.61 0.72 0.12 0.16 nm59 OTL_ 0.52 0.56 0.15 0.10 nm60 CD4 + CD4 + CD8 + Th Th Crypto- Marker- CD4 + Central Effect. toxic ID Th2 Mem. Mem. T-Cells OTL_ 0.02 0.03 0.03 0.03 nm18 OTL_ 0.02 0.03 0.02 0.18 nm19 OTL_ 0.04 0.05 0.07 0.09 nm5 OTL_ 0.04 0.04 0.05 0.04 nm4 OTL_ 0.05 0.04 0.04 0.05 nm22 OTL_ 0.03 0.05 0.02 0.12 nm23 OTL_ 0.05 0.02 0.04 0.03 nm24 OTL_ 0.05 0.04 0.06 0.06 nm25 OTL_ 0.09 0.08 0.10 0.09 nm26 OTL_ 0.05 0.04 0.07 0.05 nm27 OTL_ 0.07 0.08 0.09 0.06 nm28 OTL_ 0.07 0.06 0.09 0.12 nm29 OTL_ 0.10 0.11 0.10 0.16 nm30 OTL_ 0.06 0.09 0.06 0.10 nm31 OTL_ 0.04 0.05 0.05 0.12 nm32 OTL_ 0.03 0.04 0.04 0.10 nm33 OTL_ 0.12 0.13 0.13 0.11 nm34 OTL_ 0.05 0.05 0.06 0.04 nm35 OTL_ 0.10 0.10 0.13 0.10 nm36 OTL_ 0.09 0.08 0.15 0.11 nm37 OTL_ 0.08 0.07 0.08 0.08 nm38 OTL_ 0.13 0.12 0.14 0.12 nm39 OTL_ 0.05 0.04 0.06 0.08 nm40 OTL_ 0.08 0.10 0.11 0.11 nm41 OTL_ 0.11 0.10 0.14 0.14 nm42 OTL_ 0.04 0.07 0.09 0.09 nm43 OTL_ 0.08 0.07 0.11 0.13 nm44 OTL_ 0.12 0.13 0.10 0.16 nm45 OTL_ 0.04 0.03 0.06 0.04 nm46 OTL_ 0.05 0.05 0.06 0.12 nm47 OTL_ 0.05 0.05 0.07 0.09 nm48 OTL_ 0.13 0.12 0.15 0.13 nm49 OTL_ 0.05 0.05 0.06 0.12 nm50 OTL_ 0.02 0.03 0.04 0.10 nm51 OTL_ 0.11 0.11 0.11 0.19 nm52 OTL_ 0.11 0.12 0.15 0.15 nm53 OTL_ 0.13 0.14 0.16 0.15 nm54 OTL_ 0.03 0.03 0.04 0.07 nm55 OTL_ 0.17 0.11 0.14 0.14 nm56 OTL_ 0.20 0.22 0.21 0.15 nm57 OTL_ 0.08 0.12 0.12 0.15 nm58 OTL_ 0.15 0.13 0.18 0.13 nm59 OTL_ 0.13 0.13 0.17 0.12 nm60 Marker- NK ID T-Cells Discovery Fragment OTL_ 0.07 GGCTTGCGTAGT nm18 CAAGGCTGCCCG CGTGCCACGTGT GGTGGACAGCA TCG OTL_ 0.05 CGCGCCTAGCTG nm19 GCACTCCATTCA TTGCGGACACAG CCGAGCCCTCCG GG OTL_ 0.08 AGTCATCTGTTT nm5 TGCTTTTTTTCC AGAAGTAGTAA GTCTGCTGGCCT CCG OTL_ 0.06 CGGAAAAACAA nm4 AAGGCATCTGCA CCTGCAGCCCTG CTGAGGCCCCTG CTG OTL_ 0.10 GCATGGGTTCTG nm22 ATGGGGGCCCTG CCATAGGCCGCC TGGTGACCCACG CG OTL_ 0.25 CGCACATCTCAT nm23 GAATGCCATGGT ATTCCTTATTTC GTGTCAGCCCTT CC OTL_ 0.08 CGCACCCAGCCG nm24 CACCTACTCTTT TGTAAAGCACCT GTGACAATGAA GGA OTL_ 0.07 CAAGCCCCAGG nm25 GCTCCTTGAGGA AACAACAGGGG TGCCAGACGTGG CCCG OTL_ 0.16 CGGGGGAGGCT nm26 GCTGAGTGGTTT TGAAATTATACA GAGCTGGATTTG AAC OTL_ 0.06 CTTCTGTCGTTT nm27 CAATTGGCATCT GGTGAACTATGC CTAACAGCTTAA CG OTL_ 0.08 GGAGTTCATTGC nm28 TGGGTGTGACTG GAGAGGTCAGG CAGGAGCTCTCA TCG OTL_ 0.16 AGATTTTCCCTA nm29 GCCCTGCAGCTG CCCTCCATGGAT GGACTTGTATCT CG OTL_ 0.17 CTGCTGTTCAGG nm30 GAAATGGCTTCC TTTCAGATGTGT TTCTCATAGTCT CG OTL_ 0.10 GGCGGGACGCT nm31 GTTTCGACACTG CAGGTAGGGTGT AAGGATTGCTCA TCG OTL_ 0.23  TGCCTGAAATGA nm32 TACAGTAGTGTA TAAACCAAGTAT CTCTGCTTGCAT CG OTL_ 0.10  CGGTTTGCATCT nm33 CCAGCCCCCGCG GCTCACAGGCCG TGTAACTTCACT GC OTL_ 0.10  CGGCCATATTCT nm34 GGCAGGGTCAG TGGCTCCAACTA ACATTTGTTTGG TAC OTL_ 0.05  CGAAGAATTGTA nm35 TTTGCATGTCTG AAATGAAAGCC CAGAGAATAGG GTGG OTL_ 0.17  TGGAAACCCCTT nm36 CAGCAGCGTATG GTGCTGGGGACC TTCTGGGGAGAT CG OTL_ 0.22  AAAGCATGCAG nm37 CGTGGAGGGCT GGTCCAGGTCAG GTGGCATCAAA GAGCG OTL_ 0.20  CGGTACCCCAAA nm38 ATTTGGTGCTTT GACATGCTGAAC TAGAGAAGCAG CCG OTL_ 0.16  CGCATTCTTGCT nm39 CCCGAATACTAG CCAAGTCCCTAC AGAGGCTGATCC CG OTL_ 0.11 GCAGCCTCTGGG nm40 TGGGTGGCGGA GGCTGAGGCGA TGCTGTCCACCA CACG OTL_ 0.15 CGAGTCTGAACC nm41 ATCTCAACTCAG AAAACACCAGA AGAAAAAGTGT GGAG OTL_ 0.15 CGGTGTTTCTGC nm42 ACTGTTGATCCT GCTCTCGTCTCT GGCTACCCCCAC TG OTL_ 0.19 CGCTGAAACTTA nm43 GCAGGCACTCA GTAAATATTTTG CTAAGCAGTTAA AAC OTL_ 0.20 CGCCTGCAGAA nm44 AGTGATCTTTCC GAGACAGGACG ATGTGCTCATCT CCTT OTL_ 0.19 AGTCAAAGTCA nm45 AATCATGGGTAG ATTCCGTCACTA ACAAAGTGAGC CACG OTL_ 0.13 CGTCCTGAGTTC nm46 CCAGACGTCATA GGTGCTTGCTCA ACGAGTGTTTGA AT OTL_ 0.20 CTACCAAAGCAC nm47 TGGAGCTCATAA CAAGCTGCCTGT CCTTGGCCACCT CG OTL_ 0.23 CCACTGGAGATA nm48 TACTCTACCCTG GGGAGTTAAGA TAATTGTGAGCA CCG OTL_ 0.14 CGGGCTGGGGA nm49 GGTGTAAAGAC AAATCCCGGTGA CCCTGGCCCTAA AAAG OTL_ 0.21 CGCGCGTGCTTT nm50 TGAGAAGGCAT ATGCTGGGTGTG TCTGTCTGTGCC TAT OTL_ 0.24 ACGCTAGTGCAG nm51 CACTTTTGAAAG TAAAAAGCACTT TGCAATAATTAA CG OTL_ 0.14 CGTCGTCCTGGC nm52 TAGGATCTAGCA TCTCAGTGCAAA ATGGGCTATGTA AG OTL_ 0.23 AGCCCGGGGTG nm53 CAGGACTCAGA CAGAAACCTCA GGGAGGCGGGG CTGACG OTL_ 0.15 CGGTGATTCAAG nm54 ACCTCCAAGAAT TCCTGTGGTTCC CAGTAAATCCCC AC OTL_ 0.11 CGAGGACGCCTT nm55 AGGGACGTTTTG GGGCTTAAAGCC ACTAAAGACGTT TC OTL_ 0.13 CGCCCACACAGT nm56 TTGGAGTTAAAC AGATCTCAACAA ATGAACACAGTT AT OTL_ 0.23 CTGGTTCATCTC nm57 AGGTGTTGTTGC TTTGTGAACATT CACTAAGCTCTA CG OTL_ 0.12 TCTTCTTAGTGA nm58 GCATGCTCATAG CTAACCTTCTTT GAACTTCCTCAA CG OTL_ 0.21 CTATCGCTTGGG nm59 GCTGTTGTGAGG CCTCGGTGAGAT AACCGTGCCATG CG OTL_ 0.13 TCTCTCCTTTGC nm60 TATGGGAGGGCT TGAATCTGTGGC AGCCTTCAAAAC CG

TABLE 41 MDSC (myleoid-derived suppressor cells) Marker Basophil Marker- Target- Granu- ID ID SYMBOL Accession locytes MDSC_ cg103 UPP1 NM_ 0.97 nm1 117717 001287426 MDSC_ cg093 DAXX NM_ 0.96 nm2 65002 001141969 MDSC_ cg224 M4SF19 NM_ 0.94 nm3 96559 001204897 MDSC_ cg249 SRC NM_ 0.79 nm4  56391 005417 MDSC_ cg227 TYH3 NM_ 0.91 nm5 88953 025250 MDSC_ cg064 CLCN7 NM_ 0.91 nm6 89615 001114331 MDSC_ cg189 — — 0.93 nm7 95788 MDSC_ cg131 SMURF1 NM_ 0.91 nm8 52501 001199847 MDSC_ cg181 — — 0.88 nm9 29996 MDSC_ cg207 — — 0.97 nm10 00740 MDSC_ cg023 ZC3H8 NM_ 0.90 nm11 41139 032494 MDSC_ cg199 SYNPO NM_ 0.84 nm12 84911 001109974 MDSC_ cg221 ATP6V1E2 NM_ 0.90 nm13 37471 080653 MDSC_ cg088 SNX29 NM_ 0.84 nm14 22891 032167 MDSC_ cg004 ATN1 NM_ 0.89 nm15 76608 001007026 MDSC_ cg202 CTSZ NM_ 0.89 nm16 78790 001336 MDSC_ cg086 — — 0.91 nm17 97732 MDSC_ cg008 CMIP NM_ 0.87 nm18 64293 030629 MDSC_ cg144 GPNMB NM_ 0.87 nm19 44376 001005340 MDSC_ cg009 — — 0.88 nm20 45409 MDSC_ cg033 PDXK NM_ 0.86 nm21 66992 003681 MDSC_ cg041 DOT1L NM_ 0.72 nm22 43586 032482 MDSC_ cg004 — — 0.85 nm23 26089 MDSC_ cg108 CGF3 NM_ 0.34 nm24 64200 006315 MDSC_ cg042 — — 0.85 nm25 52044 MDSC_ cg019 — — 0.84 nm26 05967 MDSC_ cg035 — — 0.90 nm27 00164 MDSC_ cg017 NANOG NM_ 0.90 nm28 34240 024865 MDSC_ cg091 TRIM35 NM_ 0.77 nm29 27592 171982 MDSC_ cg090 CCR1 NM_ 0.82 nm30 88625 001295 MDSC_ cg176 APBB2 NM_ 0.88 nm31 99214 001166050 MDSC_ cg079 MFSD12 NM_ 0.71 nm32 37803 001042680 MDSC_ cg272 HS1BP3 NM_ 0.81 nm33 82397 022460 MDSC_ cg013 RXRB NM_ 0.84 nm34 59676 001270401 MDSC_ cg054 PHF15 NM_ 0.75 nm35 76182 015288 MDSC_ cg148 SORCS2 NM_ 0.80 nm36 12474 020777 MDSC_ cg082 — — 0.89 nm37 10681 MDSC_ cg170 ITGAE NM_ 0.96 nm38 74014 002208 MDSC_ cg153 MRAS NM_ 0.84 nm39 20001 001085059 MDSC_ cg193 — — 0.85 nm40 99285 MDSC_ cg211 — — 0.81 nm41 64050 MDSC_ cg212 RGIC1 NM_ 0.79 nm42 04530 001031711 MDSC_ cg072 CSF1R NM_ 0.80 nm43 60017 001288705 MDSC_ cg061 AC10480 — 0.87 nm44 93597 9.3 MDSC_ cg261 — — 0.73 nm45 74398 MDSC_ cg245 SH3RF3 NM_ 0.83 nm46 87185 001099289 MDSC_ cg058 MFSD7 NM_ 0.89 nm47 27190 032219 MDSC_ cg031 — — 0.80 nm48 76993 MDSC_ cg033 MBNL2 NM_ 0.72 nm49 72334 144778 MDSC_ cg218 SPARC NM_ 0.80 nm50 77464 003118 MDSC_ cg098 FKBP2 NM_ 0.90 nm51 54726 001135208 MDSC_ cg164 BCAT1 NM_ 0.86 nm52 90209 001178091 MDSC_ cg181 — — 0.80 nm53 14313 MDSC_ cg223 — — 0.64 nm54 07974 MDSC_ cg191 AMPD3 NM_ 0.63 nm55 32462 000480 MDSC_ cg122 MYO9B NM_ 0.68 nm56 29979 001130065 MDSC_ cg060 — — 0.82 nm57 93152 Eosino- Neutro- Non phil phil Classical classical Marker- Granu- Granu- Mono- Mono- ID locytes locytes cytes cytes MDSC_ 0.95 0.95 0.95 0.93 nm1 MDSC_ 0.96 0.92 0.88 0.90 nm2 MDSC_ 0.95 0.95 0.92 0.80 nm3 MDSC_ 0.82 0.87 0.77 0.54 nm4  MDSC_ 0.84 0.89 0.83 0.84 nm5 MDSC_ 0.88 0.87 0.85 0.77 nm6 MDSC_ 0.90 0.92 0.65 0.63 nm7 MDSC_ 0.91 0.91 0.81 0.81 nm8 MDSC_ 0.89 0.90 0.90 0.90 nm9 MDSC_ 0.81 0.02 0.51 0.59 nm10 MDSC_ 0.91 0.92 0.87 0.88 nm11 MDSC_ 0.90 0.82 0.72 0.76 nm12 MDSC_ 0.87 0.90 0.87 0.84 nm13 MDSC_ 0.77 0.51 0.72 0.76 nm14 MDSC_ 0.85 0.38 0.55 0.56 nm15 MDSC_ 0.89 0.90 0.72 0.56 nm16 MDSC_ 0.91 0.92 0.79 0.62 nm17 MDSC_ 0.82 0.82 0.87 0.87 nm18 MDSC_ 0.90 0.91 0.73 0.59 nm19 MDSC_ 0.88 0.88 0.88 0.87 nm20 MDSC_ 0.81 0.65 0.76 0.75 nm21 MDSC_ 0.08 0.21 0.73 0.38 nm22 MDSC_ 0.89 0.87 0.87 0.82 nm23 MDSC_ 0.47 0.60 0.58 0.65 nm24 MDSC_ 0.83 0.82 0.63 0.40 nm25 MDSC_ 0.85 0.85 0.83 0.82 nm26 MDSC_ 0.89 0.86 0.66 0.71 nm27 MDSC_ 0.90 0.88 0.57 0.58 nm28 MDSC_ 0.76 0.70 0.81 0.79 nm29 MDSC_ 0.87 0.89 0.87 0.83 nm30 MDSC_ 0.89 0.86 0.82 0.76 nm31 MDSC_ 0.51 0.90 0.90 0.85 nm32 MDSC_ 0.85 0.85 0.68 0.46 nm33 MDSC_ 0.87 0.86 0.88 0.87 nm34 MDSC_ 0.78 0.76 0.66 0.63 nm35 MDSC_ 0.83 0.85 0.82 0.74 nm36 MDSC_ 0.89 0.91 0.66 0.45 nm37 MDSC_ 0.67 0.03 0.42 0.49 nm38 MDSC_ 0.85 0.81 0.56 0.48 nm39 MDSC_ 0.86 0.86 0.83 0.86 nm40 MDSC_ 0.85 0.85 0.77 0.78 nm41 MDSC_ 0.84 0.82 0.86 0.88 nm42 MDSC_ 0.87 0.86 0.83 0.62 nm43 MDSC_ 0.82 0.81 0.87 0.86 nm44 MDSC_ 0.67 0.79 0.72 0.51 nm45 MDSC_ 0.84 0.85 0.81 0.72 nm46 MDSC_ 0.79 0.63 0.60 0.39 nm47 MDSC_ 0.79 0.73 0.58 0.42 nm48 MDSC_ 0.68 0.69 0.70 0.69 nm49 MDSC_ 0.73 0.32 0.48 0.44 nm50 MDSC_ 0.72 0.82 0.71 0.36 nm51 MDSC_ 0.80 0.73 0.61 0.51 nm52 MDSC_ 0.75 0.64 0.52 0.44 nm53 MDSC_ 0.43 0.50 0.49 0.41 nm54 MDSC_ 0.06 0.07 0.44 0.37 nm55 MDSC_ 0.39 0.76 0.63 0.53 nm56 MDSC_ 0.53 0.47 0.48 0.33 nm57 NK NK Marker Clas- bright NK ID- sical NK B_1 NK B_2 bright MDSC_ 0.95 0.96 0.93 0.94 nm1 MDSC_ 0.96 0.96 0.95 0.95 nm2 MDSC_ 0.76 0.91 0.86 0.88 nm3 MDSC_ 0.93 0.91 0.78 0.85 nm4  MDSC_ 0.95 0.89 0.88 0.89 nm5 MDSC_ 0.92 0.91 0.93 0.92 nm6 MDSC_ 0.95 0.95 0.97 0.96 nm7 MDSC_ 0.91 0.92 0.89 0.91 nm8 MDSC_ 0.89 0.89 0.89 0.89 nm9 MDSC_ 0.98 0.98 0.95 0.96 nm10 MDSC_ 0.90 0.90 0.84 0.87 nm11 MDSC_ 0.89 0.92 0.89 0.90 nm12 MDSC_ 0.87 0.89 0.89 0.89 nm13 MDSC_ 0.90 0.89 0.90 0.90 nm14 MDSC_ 0.92 0.90 0.92 0.91 nm15 MDSC_ 0.89 0.86 0.83 0.84 nm16 MDSC_ 0.88 0.89 0.88 0.89 nm17 MDSC_ 0.89 0.90 0.88 0.89 nm18 MDSC_ 0.87 0.83 0.81 0.82 nm19 MDSC_ 0.87 0.89 0.81 0.85 nm20 MDSC_ 0.86 0.83 0.87 0.85 nm21 MDSC_ 0.90 0.96 0.95 0.95 nm22 MDSC_ 0.85 0.79 0.75 0.77 nm23 MDSC_ 0.88 0.88 0.86 0.87 nm24 MDSC_ 0.87 0.90 0.89 0.90 nm25 MDSC_ 0.87 0.88 0.87 0.87 nm26 MDSC_ 0.84 0.74 0.80 0.77 nm27 MDSC_ 0.87 0.81 0.74 0.78 nm28 MDSC_ 0.83 0.86 0.79 0.82 nm29 MDSC_ 0.81 0.64 0.74 0.69 nm30 MDSC_ 0.89 0.88 0.87 0.88 nm31 MDSC_ 0.90 0.88 0.89 0.88 nm32 MDSC_ 0.84 0.81 0.88 0.84 nm33 MDSC_ 0.85 0.83 0.84 0.83 nm34 MDSC_ 0.84 0.85 0.82 0.84 nm35 MDSC_ 0.83 0.75 0.71 0.73 nm36 MDSC_ 0.85 0.82 0.82 0.82 nm37 MDSC_ 0.84 0.89 0.89 0.89 nm38 MDSC_ 0.81 0.81 0.81 0.81 nm39 MDSC_ 0.86 0.88 0.85 0.86 nm40 MDSC_ 0.83 0.84 0.85 0.85 nm41 MDSC_ 0.78 0.85 0.85 0.85 nm42 MDSC_ 0.77 0.83 0.84 0.83 nm43 MDSC_ 0.84 0.90 0.92 0.91 nm44 MDSC_ 0.79 0.83 0.84 0.84 nm45 MDSC_ 0.70 0.75 0.73 0.74 nm46 MDSC_ 0.88 0.91 0.87 0.89 nm47 MDSC_ 0.83 0.84 0.79 0.81 nm48 MDSC_ 0.83 0.79 0.80 0.79 nm49 MDSC_ 0.83 0.84 0.83 0.83 nm50 MDSC_ 0.88 0.88 0.82 0.85 nm51 MDSC_ 0.77 0.86 0.80 0.83 nm52 MDSC_ 0.83 0.83 0.84 0.84 nm53 MDSC_ 0.74 0.69 0.69 0.69 nm54 MDSC_ 0.84 0.87 0.81 0.84 nm55 MDSC_ 0.63 0.76 0.66 0.71 nm56 MDSC_ 0.78 0.85 0.82 0.84 nm57 Marker B- CD4 + CD4 + ID- Cells MDSC Th naive act. MDSC_ 0.97 0.15 0.95 0.92 nm1 MDSC_ 0.96 0.21 0.96 0.95 nm2 MDSC_ 0.82 0.28 0.93 0.91 nm3 MDSC_ 0.56 0.10 0.94 0.75 nm4  MDSC_ 0.94 0.29 0.94 0.90 nm5 MDSC_ 0.93 0.35 0.93 0.92 nm6 MDSC_ 0.98 0.21 0.98 0.87 nm7 MDSC_ 0.92 0.36 0.91 0.90 nm8 MDSC_ 0.91 0.37 0.92 0.90 nm9 MDSC_ 0.98 0.17 0.84 0.97 nm10 MDSC_ 0.90 0.28 0.92 0.88 nm11 MDSC_ 0.91 0.29 0.92 0.89 nm12 MDSC_ 0.87 0.19 0.88 0.89 nm13 MDSC_ 0.91 0.27 0.91 0.90 nm14 MDSC_ 0.88 0.25 0.91 0.86 nm15 MDSC_ 0.47 0.33 0.90 0.86 nm16 MDSC_ 0.83 0.23 0.91 0.82 nm17 MDSC_ 0.91 0.28 0.92 0.73 nm18 MDSC_ 0.84 0.22 0.93 0.81 nm19 MDSC_ 0.86 0.18 0.88 0.80 nm20 MDSC_ 0.89 0.25 0.88 0.81 nm21 MDSC_ 0.78 0.21 0.98 0.92 nm22 MDSC_ 0.62 0.33 0.89 0.81 nm23 MDSC_ 0.87 0.33 0.92 0.89 nm24 MDSC_ 0.88 0.17 0.89 0.80 nm25 MDSC_ 0.85 0.33 0.91 0.86 nm26 MDSC_ 0.87 0.23 0.91 0.75 nm27 MDSC_ 0.87 0.26 0.90 0.79 nm28 MDSC_ 0.92 0.28 0.91 0.82 nm29 MDSC_ 0.85 0.28 0.88 0.83 nm30 MDSC_ 0.90 0.16 0.91 0.70 nm31 MDSC_ 0.84 0.21 0.91 0.76 nm32 MDSC_ 0.81 0.25 0.85 0.81 nm33 MDSC_ 0.82 0.25 0.86 0.70 nm34 MDSC_ 0.85 0.26 0.88 0.80 nm35 MDSC_ 0.83 0.24 0.87 0.75 nm36 MDSC_ 0.83 0.13 0.88 0.73 nm37 MDSC_ 0.98 0.19 0.93 0.68 nm38 MDSC_ 0.81 0.28 0.87 0.84 nm39 MDSC_ 0.83 0.28 0.88 0.66 nm40 MDSC_ 0.82 0.25 0.91 0.73 nm41 MDSC_ 0.85 0.21 0.85 0.67 nm42 MDSC_ 0.82 0.22 0.88 0.63 nm43 MDSC_ 0.55 0.16 0.78 0.42 nm44 MDSC_ 0.70 0.14 0.84 0.61 nm45 MDSC_ 0.83 0.19 0.84 0.57 nm46 MDSC_ 0.83 0.25 0.90 0.71 nm47 MDSC_ 0.81 0.18 0.88 0.78 nm48 MDSC_ 0.76 0.19 0.70 0.88 nm49 MDSC_ 0.84 0.20 0.86 0.74 nm50 MDSC_ 0.55 0.19 0.91 0.68 nm51 MDSC_ 0.87 0.21 0.87 0.74 nm52 MDSC_ 0.35 0.21 0.88 0.70 nm53 MDSC_ 0.69 0.17 0.81 0.71 nm54 MDSC_ 0.51 0.15 0.73 0.82 nm55 MDSC_ 0.71 0.15 0.88 0.74 nm56 MDSC_ 0.75 0.14 0.90 0.59 nm57 CD4 + CD4 + Th Th Marker CD4 + CD4 + Central EFFECT. ID- Th1 Th2 Mem. Mem. MDSC_ 0.93 0.95 0.96 0.95 nm1 MDSC_ 0.96 0.97 0.97 0.96 nm2 MDSC_ 0.93 0.94 0.93 0.94 nm3 MDSC_ 0.82 0.82 0.85 0.84 nm4  MDSC_ 0.92 0.92 0.94 0.95 nm5 MDSC_ 0.92 0.92 0.92 0.92 nm6 MDSC_ 0.90 0.92 0.95 0.95 nm7 MDSC_ 0.91 0.90 0.91 0.91 nm8 MDSC_ 0.89 0.89 0.91 0.90 nm9 MDSC_ 0.98 0.98 0.97 0.98 nm10 MDSC_ 0.86 0.88 0.90 0.88 nm11 MDSC_ 0.90 0.89 0.91 0.90 nm12 MDSC_ 0.88 0.88 0.88 0.88 nm13 MDSC_ 0.86 0.89 0.87 0.88 nm14 MDSC_ 0.89 0.89 0.90 0.90 nm15 MDSC_ 0.87 0.89 0.89 0.89 nm16 MDSC_ 0.85 0.87 0.85 0.87 nm17 MDSC_ 0.73 0.77 0.78 0.77 nm18 MDSC_ 0.87 0.88 0.88 0.86 nm19 MDSC_ 0.81 0.84 0.84 0.85 nm20 MDSC_ 0.84 0.83 0.83 0.84 nm21 MDSC_ 0.96 0.96 0.96 0.96 nm22 MDSC_ 0.84 0.85 0.86 0.87 nm23 MDSC_ 0.93 0.93 0.93 0.94 nm24 MDSC_ 0.85 0.87 0.85 0.81 nm25 MDSC_ 0.87 0.89 0.84 0.81 nm26 MDSC_ 0.86 0.89 0.91 0.91 nm27 MDSC_ 0.83 0.84 0.84 0.82 nm28 MDSC_ 0.88 0.88 0.88 0.86 nm29 MDSC_ 0.86 0.85 0.86 0.86 nm30 MDSC_ 0.76 0.77 0.74 0.76 nm31 MDSC_ 0.76 0.79 0.83 0.81 nm32 MDSC_ 0.82 0.83 0.82 0.83 nm33 MDSC_ 0.75 0.74 0.75 0.75 nm34 MDSC_ 0.81 0.82 0.81 0.81 nm35 MDSC_ 0.79 0.79 0.78 0.79 nm36 MDSC_ 0.82 0.83 0.85 0.83 nm37 MDSC_ 0.93 0.92 0.92 0.91 nm38 MDSC_ 0.80 0.82 0.83 0.83 nm39 MDSC_ 0.76 0.69 0.77 0.73 nm40 MDSC_ 0.69 0.80 0.82 0.74 nm41 MDSC_ 0.63 0.68 0.71 0.69 nm42 MDSC_ 0.67 0.66 0.67 0.68 nm43 MDSC_ 0.62 0.65 0.45 0.13 nm44 MDSC_ 0.65 0.57 0.64 0.61 nm45 MDSC_ 0.54 0.64 0.66 0.63 nm46 MDSC_ 0.77 0.77 0.79 0.79 nm47 MDSC_ 0.75 0.82 0.81 0.81 nm48 MDSC_ 0.80 0.80 0.74 0.87 nm49 MDSC_ 0.75 0.78 0.79 0.80 nm50 MDSC_ 0.71 0.75 0.78 0.79 nm51 MDSC_ 0.61 0.80 0.77 0.72 nm52 MDSC_ 0.64 0.77 0.72 0.70 nm53 MDSC_ 0.76 0.81 0.77 0.81 nm54 MDSC_ 0.76 0.81 0.77 0.76 nm55 MDSC_ 0.77 0.73 0.72 0.72 nm56 MDSC_ 0.59 0.69 0.68 0.63 nm57 CD8 + CD4 + Cytoto- CD8 + Marker NK CD4 + toxic naive ID- T cells TFH T-cells T8n_1 MDSC_ 0.83 0.90 0.96 0.94 nm1 MDSC_ 0.92 0.94 0.97 0.96 nm2 MDSC_ 0.79 0.91 0.87 0.93 nm3 MDSC_ 0.80 0.62 0.93 0.91 nm4  MDSC_ 0.88 0.90 0.95 0.94 nm5 MDSC_ 0.91 0.91 0.93 0.90 nm6 MDSC_ 0.88 0.91 0.95 0.96 nm7 MDSC_ 0.90 0.88 0.92 0.91 nm8 MDSC_ 0.90 0.90 0.91 0.88 nm9 MDSC_ 0.94 0.97 0.96 0.93 nm10 MDSC_ 0.84 0.89 0.91 0.89 nm11 MDSC_ 0.89 0.91 0.92 0.90 nm12 MDSC_ 0.89 0.89 0.89 0.88 nm13 MDSC_ 0.78 0.88 0.91 0.91 nm14 MDSC_ 0.88 0.89 0.90 0.90 nm15 MDSC_ 0.84 0.87 0.89 0.90 nm16 MDSC_ 0.87 0.86 0.86 0.91 nm17 MDSC_ 0.76 0.68 0.87 0.91 nm18 MDSC_ 0.78 0.84 0.89 0.86 nm19 MDSC_ 0.78 0.83 0.86 0.86 nm20 MDSC_ 0.84 0.80 0.87 0.87 nm21 MDSC_ 0.92 0.93 0.97 0.95 nm22 MDSC_ 0.76 0.81 0.89 0.84 nm23 MDSC_ 0.87 0.87 0.93 0.90 nm24 MDSC_ 0.82 0.71 0.91 0.87 nm25 MDSC_ 0.76 0.89 0.86 0.87 nm26 MDSC_ 0.75 0.79 0.90 0.80 nm27 MDSC_ 0.79 0.79 0.86 0.87 nm28 MDSC_ 0.80 0.82 0.66 0.44 nm29 MDSC_ 0.77 0.83 0.85 0.86 nm30 MDSC_ 0.76 0.74 0.83 0.88 nm31 MDSC_ 0.80 0.85 0.84 0.90 nm32 MDSC_ 0.84 0.82 0.85 0.83 nm33 MDSC_ 0.73 0.61 0.86 0.85 nm34 MDSC_ 0.76 0.77 0.87 0.87 nm35 MDSC_ 0.68 0.77 0.83 0.82 nm36 MDSC_ 0.80 0.75 0.84 0.87 nm37 MDSC_ 0.86 0.81 0.80 0.84 nm38 MDSC_ 0.78 0.83 0.80 0.78 nm39 MDSC_ 0.76 0.69 0.79 0.87 nm40 MDSC_ 0.73 0.75 0.82 0.87 nm41 MDSC_ 0.70 0.61 0.76 0.85 nm42 MDSC_ 0.61 0.68 0.79 0.86 nm43 MDSC_ 0.79 0.55 0.52 0.91 nm44 MDSC_ 0.71 0.59 0.76 0.84 nm45 MDSC_ 0.52 0.54 0.77 0.82 nm46 MDSC_ 0.78 0.74 0.83 0.89 nm47 MDSC_ 0.78 0.70 0.85 0.87 nm48 MDSC_ 0.68 0.72 0.56 0.85 nm49 MDSC_ 0.75 0.78 0.82 0.87 nm50 MDSC_ 0.68 0.70 0.82 0.89 nm51 MDSC_ 0.68 0.77 0.79 0.89 nm52 MDSC_ 0.71 0.73 0.80 0.87 nm53 MDSC_ 0.65 0.73 0.81 0.77 nm54 MDSC_ 0.68 0.82 0.86 0.87 nm55 MDSC_ 0.74 0.66 0.79 0.84 nm56 MDSC_ 0.61 0.45 0.76 0.88 nm57 CD8 + CD8 + Th Th Marker CD8 + Central  Effect. ID- act. Mem. Mem. TEMRA MDSC_ 0.95 0.94 0.95 0.94 nm1 MDSC_ 0.95 0.96 0.96 0.96 nm2 MDSC_ 0.92 0.82 0.88 0.60 nm3 MDSC_ 0.83 0.88 0.87 0.91 nm4  MDSC_ 0.91 0.88 0.93 0.95 nm5 MDSC_ 0.92 0.90 0.91 0.90 nm6 MDSC_ 0.83 0.92 0.88 0.87 nm7 MDSC_ 0.90 0.91 0.91 0.90 nm8 MDSC_ 0.90 0.87 0.88 0.87 nm9 MDSC_ 0.97 0.98 0.97 0.98 nm10 MDSC_ 0.88 0.89 0.83 0.83 nm11 MDSC_ 0.89 0.89 0.85 0.89 nm12 MDSC_ 0.89 0.86 0.86 0.86 nm13 MDSC_ 0.91 0.90 0.88 0.87 nm14 MDSC_ 0.88 0.89 0.89 0.90 nm15 MDSC_ 0.85 0.87 0.84 0.86 nm16 MDSC_ 0.80 0.82 0.80 0.78 nm17 MDSC_ 0.80 0.89 0.86 0.87 nm18 MDSC_ 0.81 0.78 0.81 0.83 nm19 MDSC_ 0.79 0.80 0.78 0.64 nm20 MDSC_ 0.84 0.86 0.79 0.84 nm21 MDSC_ 0.92 0.88 0.94 0.97 nm22 MDSC_ 0.83 0.80 0.78 0.83 nm23 MDSC_ 0.92 0.86 0.91 0.89 nm24 MDSC_ 0.85 0.90 0.82 0.85 nm25 MDSC_ 0.86 0.87 0.71 0.45 nm26 MDSC_ 0.78 0.76 0.78 0.78 nm27 MDSC_ 0.80 0.77 0.84 0.86 nm28 MDSC_ 0.80 0.83 0.89 0.86 nm29 MDSC_ 0.84 0.81 0.49 0.84 nm30 MDSC_ 0.74 0.78 0.75 0.78 nm31 MDSC_ 0.70 0.84 0.72 0.68 nm32 MDSC_ 0.81 0.79 0.78 0.77 nm33 MDSC_ 0.78 0.78 0.79 0.82 nm34 MDSC_ 0.85 0.79 0.79 0.83 nm35 MDSC_ 0.79 0.79 0.76 0.81 nm36 MDSC_ 0.72 0.75 0.69 0.76 nm37 MDSC_ 0.56 0.80 0.83 0.96 nm38 MDSC_ 0.83 0.79 0.76 0.81 nm39 MDSC_ 0.61 0.66 0.67 0.77 nm40 MDSC_ 0.72 0.78 0.62 0.52 nm41 MDSC_ 0.73 0.71 0.70 0.78 nm42 MDSC_ 0.62 0.69 0.67 0.67 nm43 MDSC_ 0.38 0.88 0.82 0.67 nm44 MDSC_ 0.65 0.72 0.62 0.60 nm45 MDSC_ 0.57 0.66 0.55 0.56 nm46 MDSC_ 0.75 0.77 0.75 0.79 nm47 MDSC_ 0.85 0.82 0.80 0.77 nm48 MDSC_ 0.88 0.81 0.85 0.86 nm49 MDSC_ 0.69 0.78 0.76 0.76 nm50 MDSC_ 0.70 0.73 0.69 0.62 nm51 MDSC_ 0.72 0.67 0.61 0.59 nm52 MDSC_ 0.70 0.79 0.69 0.63 nm53 MDSC_ 0.73 0.70 0.73 0.73 nm54 MDSC_ 0.84 0.85 0.78 0.77 nm55 MDSC_ 0.75 0.72 0.70 0.61 nm56 MDSC_ 0.65 0.69 0.52 0.68 nm57 CD8 + Marker NK NK ID- T cells T-Cells Discovery Fragment MDSC_ 0.88 0.89 CGCCTGGAGC nm1 GCCTCCCACTG CAGACGTCTGT CCGCCTCCAGC CGCTCTC MDSC_ 0.95 0.96 CGCCGGGCCA nm2 ACACAGGATCT GATAGTGCAG GGTCAACGCCT ACGTGGGA MDSC_ 0.59 0.72 CGCGCCCCCAC nm3 GCCCCTGCCCA CAGGCCTGCAT TGAAGGCGCTT CCGCTC MDSC_ 0.81 0.87 AAGGATGGCA nm4  TCCATCCGTAA AGGGCTTCCTC GGTCCAGCGCC AGGAACG MDSC_ 0.93 0.93 CGCGGCCGAG nm5 CTGTCTGTCCA AGCCTGGGCCC CAGCACCCAG CGCAAGCT MDSC_ 0.91 0.91 GAGTGTTGGCT nm6 CACGTGTTCCT GAGCCTGTCTG TTTTTAGTTAG TGTCCG MDSC_ 0.85 0.90 CGGGCAGATA nm7 CGAGCAGATT GACTCGCCAG GACTGTCATTG GGCCACCGC MDSC_ 0.91 0.91 CTGACCTCATC nm8 CCGGAGGCCG CTTCAGTTCTC GAATGGATGTC TCTTCCG MDSC_ 0.89 0.90 CGCCACAGGA nm9 ATGGCTCTTAT GATCCTTTTGG ATGGCTAGATT TCTGAAA MDSC_ 0.97 0.98 CCTCCTGTGAG nm10 CAACCTTTCGG CGTCTGCAGAG CTCGTGGCGTA AGAGCG MDSC_ 0.82 0.85  CGACAGCAAT nm11 CCCGTGAGAA ACTGTGGGAC AGAACCACCC AGCTAAGCAG MDSC_ 0.88  0.89 CGGCAAAGGC nm12 AGCCAATTGCT TGGCTGACGA AGCCAGGAAA ATCCCACAT MDSC_ 0.88 0.88 AAAGAATGAG nm13 GTCACTGTCAC CAATGAAGTC ACCACTGCATG ATTCATCG MDSC_ 0.87 0.88 TGTGGATTCCT nm14 CCAAACTGTGA TTGCTACATCT TAATTTTTCAGC AGGACG MDSC_ 0.90 0.90 AGATACTGGG nm15 GGACGTGCTTC GGTTGTCCTGG TCGATATCCCT AGGGTCG MDSC_ 0.86 0.88 TGGCAAGTCGC nm16 TCATGGAAACC ATTAGTGTCCA TCAGTCATCAG AAGGCG MDSC_ 0.75 0.76 CCATAGCACCC nm17 CCATAATAAA GCAGCCCGTG AGGGCAGCCT GGCTGTTCG MDSC_ 0.83 0.84 CGGAGCAGGC nm18 CACAGTCAGG GTGGAAGAAA ACGAGGGAAG ACTGAGAAAC MDSC_ 0.77 0.85 CGGCACTGCCT nm19 GATCTGGTCTC TCAAGTTCAAC CTCTTACAACT CATGTG MDSC_ 0.79 0.80 GCCTTGTCCTG nm20 GGGCTGAGCA GTGGTGCAACC CAGCCCTGAG GAATTCCG MDSC_ 0.85 0.85 CCACCTGAGGT nm21 GAGCAATCAG AGGACACCCCT CGAGTCACTGG GAGTTCG MDSC_ 0.90 0.96 CGGCACGTCC nm22 CGCCCACCACT AGAAAGCCCG CTCCCGCCAGC TCTCGCC MDSC_ 0.74 0.85 AGCTTTGTATA nm23 GATGCATGCAC TTGGAAACCA GCAAAGCTAA AAATACCG MDSC_ 0.93 0.93 CGCAGGAGCG nm24 CACACACGTTC CCACACGCCAC TCAATTCCAGA ACAACGG MDSC_ 0.85 0.86 GTATGTGTGAG nm25 TCAATCTAATG TGCCCTCCCTC AGCATAATCCT GTCACG MDSC_ 0.53 0.66 TGGAAATCTCT nm26 TTCGTCAAGGC CTCTAGTGACC GCTGGGGATTC TTCTCG MDSC_ 0.74 0.76 TCATACATTTC nm27 AACTTGCTGCT GTTCTGAGTAG GGTGATGAAAT CTTGCG MDSC_ 0.81 0.82 CGGAGTAGTCT nm28 TGAAAGACAT GACAAATCAC CAGACCTGGG AAGAAGCTA MDSC_ 0.85 0.90 GGCGGCGGGG nm29 CACAGCGTGG GGGTGTGCAGT GACTGAGAGA TGGTTCACG MDSC_ 0.68 0.64 GAATGATCTCT nm30 GCACTGTAGG ACATCCTTGGC CCTGCCTACCA AATGACG MDSC_ 0.80 0.78 CGGCTGTTCCA nm31 GACCCTAATGA GTTCAGTTGTC CTACAAAGCA GGAAGAG MDSC_ 0.71 0.69 CGGGGTGTCAC nm32 TCCTACAAGAC AAGAAAAGCC CAGGATTGCTG GCCAATG MDSC_ 0.80 0.82 ATACACAGTTC nm33 CCTGCACACAC TCGGCTAACTG TGACCAGGGT GAGAGCG MDSC_ 0.81 0.80 ATGACCCTGTG nm34 ACTAACATCTG TCAGGCAGCTG ACAAACAGCT ATTCACG MDSC_ 0.81 0.81 CTGTTAGGCAG nm35 AGCAGCCTAAT GGGAGCAGTG TGACTCATGGA CCTCACG MDSC_ 0.77 0.76 TCATCCAAGCT nm36 TGTGTGAGTCA CAATGAGCAG AAAGCATTCTT CCACCCG MDSC_ 0.64 0.77 CGGCCCCAGC nm37 ACTGCAAAGCT GTCATCGCTCC TCTCCAGGGAG CCATCCT MDSC_ 0.85 0.89 CGGCCCATGTG nm38 TCGCACTCGCC TCGGCTCCCAC ACAGCCGCCTC TGCTCC MDSC_ 0.81 0.81 CTACTTTCAAT nm39 CTCTATGGATT TCCCTATTCAG GACATTTTCTA TAAACG MDSC_ 0.73 0.74 TATGCTTACTC nm40 CCTCTCCCTCT TGTCTGTGTCC CTGTGTGGCCT GAAGCG MDSC_ 0.56 0.53 CGGAGAGCCA nm41 ACACCACCAGT GACTCACCCAA GCTGGAAATTT AAGCATC MDSC_ 0.67 0.71 CGTCTGCAAGA nm42 ACAGGGGAGA ACTAAGGTCCC AAGCAGCAAA AGTTAAAA MDSC_ 0.70 0.68 CGGCATCTTCA nm43 TTTGAGTGGGT GCGGGAAGGA CCTCATTTTGG AACCACA MDSC_ 0.83 0.74 CGCGTGCCTCT nm44 GTGCAGTCAGT GAGAAGGGCT CCCGTTCAGAA TGGGCAG MDSC_ 0.65 0.63 CGTGAGCCAG nm45 AGAGAGCTGG CTTTCAGTGTT GTCACCATGGT TACTGCTA MDSC_ 0.56 0.63 CGACTGCTCCT nm46 CTGGCAAGCA GGACCCATTTC TAAAGCATGA GTCACTAC MDSC_ 0.79 0.78 CGCTTCAGACG nm47 CATCTCTTCTC AGTGAGTCAG CTGTGGGCCCC ACTCAGG MDSC_ 0.72 0.72 CGGAAAACTT nm48 GCTAATGCTGG CTGATTCTCAT TCGTGGGTTTA CTAGTTC MDSC_ 0.85 0.70 CGCTTTATGGA nm49 GCAGCAAAGA AAGTGATTTCT TGAGATGGGTT CTACTCT MDSC_ 0.76 0.76 TAAAATTATTT nm50 TTTTCCCTAAA CCCAATCTCTC CTCTTCCTCCT CTGTCG MDSC_ 0.74 0.68 CGCTGTCAGGA nm51 ATTGTCTCCTG GTTCAACCCAC TCCTGCCTTAG GCCCAC MDSC_ 0.60 0.57 CGATGGTGAG nm52 CAAAAGGTGTT GACAGGCCTG GCATGGTGACT CACCCTG MDSC_ 0.69 0.64 TCCAAGTCAC nm53 CAGCCCTTAAA TGAGCCACCA GGTTACCTTG CATCACG MDSC_ 0.72 0.74 CGGAGGCCCA nm54 GAGAAGGGAA GTGACATGCTC AAGGTAACAC TGCTAACCA MDSC_ 0.75 0.71 CGTGAGGTTGT nm55 GTCTTACTGAG CTCCATCATA ATTCCTGTGTG CACAGA MDSC_ 0.63 0.63 CGAGGACAGT nm56 TCCTCCAGAAA TCCAGGTCAGT CACAAGACAA AGAAAAGA MDSC_ 0.57 0.47 CGGCCTCTGAG nm57 AGCTGACACG GAACTTGCATC ATTTCTGATGC

TABLE 4J Total Lymphocytes Marker Baso- Eosino- Neutro Clas- Non- phil phil phil sical classical Marker- Target- Acces- Granu- Granu- Granu- Mono- Mono- NK ID ID SYMBOL sion locytes locytes locytes cytes cytes classical LYMP_ cg1443 LTA NM_ 0.94 0.96 0.95 0.95 0.96 0.13 nm1 7551 000595 LYMP_ cg0266 KLF2 NM_0162 0.89 0.90 0.93 0.90 0.80 0.04 nm2 8248 70 LYMP_ cg0044 LIME1 NM_0178 0.78 0.68 0.89 0.78 0.72 0.03 nm3 6123 06 LYMP_ cg2195 VOPP1 NM_0307 0.84 0.81 0.89 0.87 0.84 0.08 nm4 9598 96 LYMP_ cg1716 TBCID10C NM_1985 0.83 0.82 0.81 0.79 0.73 0.08 nm5 1520 17 LYMP_ cg0396 RUNX3  NM_0010 0.61 0.77 0.85 0.85 0.79 0.08 nm6 1551 31680 LYMP_ cg0445 SLC22A23 NM_0219 0.53 0.78 0.79 0.77 0.81 0.04 nm7 0994 45 LYMP_ cg1892 LY9 NM_0010 0.81 0.83 0.83 0.68 0.63 0.08 nm8 0397 33667 LYMP_ cg1882 RAD51L1 NM_1335 0.64 0.66 0.73 0.71 0.65 0.11 nm9 5221 09 LYMP_ cg1132 C21orf70 NM_0581 0.02 0.02 0.01 0.02 0.04 0.94 nm10 7657 90 LYMP_ cg1159 — — 0.03 0.02 0.10 0.03 0.06 0.95 nm11 7902 LYMP_ cg2115 SSBP3 NM_0010 0.03 0.01 0.00 0.02 0.05 0.95 nm12 9128 09955 LYMP_ cg0532 SLCO4A1 NM_0163 0.03 0.01 0.01 0.01 0.07 0.82 nm13 7789 54 LYMP_ cg2670 CRISPLD2 NM_0314 0.19 0.03 0.03 0.04 0.09 0.96 nm14 9988 76 LYMP_ cg0526 — — 0.05 0.03 0.03 0.02 0.06 0.90 nm15 0077 LYMP_ cg1069 — — 0.13 0.24 0.06 0.02 0.06 0.95 nm16 0440 LYMP_ cg2042 ZNF516 NM_0146 0.28 0.05 0.02 0.04 0.08 0.96 nm17 9104 43 LYMP_ cg0286 UBR4 NM_0207 0.07 0.03 0.03 0.04 0.09 0.90 nm18 2467 65 LYMP_ cg0050 OSBPL5 NM_0208 0.04 0.02 0.01 0.16 0.26 0.92 nm19 0359 96 LYMP_ cg1118 — — 0.11 0.05 0.28 0.05 0.10 0.95 nm20 6858 LYMP_ cg1508 NCOR2 NM_0063 0.03 0.06 0.01 0.01 0.01 0.72 nm2l 5899 12 LYMP_ cg0840 CARS2 NM_0245 0.04 0.02 0.04 0.15 0.11 0.95 nm22 0494 37 LYMP_ cg1985 TUBGCP6 NM_0204 0.02 0.02 0.00 0.01 0.03 0.85 nm23 1816 61 LYMP_ cg2356 — — 0.05 0.04 0.02 0.05 0.10 0.89 nm24 8192 LYMP_ cg0016 ETS2 NM_0052 0.06 0.07 0.04 0.04 0.08 0.84 nm25 8694 39 LYMP_ cg0629 — — 0.07 0.10 0.04 0.04 0.09 0.90 nm26 8740 LYMP_ cg2007 BRD4 NM_0582 0.05 0.04 0.03 0.04 0.06 0.87 nm27 8972 43 LYMP_ cg2694 GFOD1  NM_0189 0.06 0.07 0.05 0.05 0.11 0.90 nm28 2829 88 LYMP_ cg0340 C16orf68 NM_0241 0.26 0.01 0.01 0.01 0.06 0.82 nm29 8945 09 LYMP_ cg0637 ERCC3 NM_0001 0.06 0.05 0.06 0.06 0.14 0.90 nm30 3940 22 LYMP_ cg2557 C14orf34 NR_0267 0.05 0.04 0.04 0.04 0.08 0.91 nm31 6997 96 LYMP_ cg1170 TFDP1 NR_0265 0.07 0.05 0.06 0.09 0.13 0.91 nm32 3212 80 LYMP_ cg0647 HTRA1 NM_0027 0.03 0.21 0.06 0.02 0.04 0.93 nm33 4225 75 LYMP_ cg0473 MYB NM_0053 0.10 0.04 0.03 0.05 0.08 0.88 nm34 9200 75 LYMP_ cg0728 HRH4 NM_0216 0.08 0.06 0.04 0.07 0.15 0.92 nm35 3015 24 LYMP_ cg1045 ETNK1  NM_0186 0.11 0.15 0.06 0.05 0.11 0.93 nm36 6459 38 LYMP_ cg2031 FER1L5 NM_0011 0.08 0.08 0.06 0.05 0.08 0.86 nm37 2012 13382 LYMP_ cg0447 ABR NM_0219 0.44 0.11 0.14 0.07 0.10 0.96 nm38 8251 62 LYMP_ cg0603 — — 0.05 0.05 0.05 0.05 0.06 0.89 nm39 0535 LYMP_ cg0771 RREB1  NM_0010 0.14 0.06 0.06 0.05 0.08 0.87 nm40 4276 03700 LYMP_ cg1734 TRIM27 NM_0065 0.26 0.05 0.02 0.02 0.05 0.89 nm41 4091 10 LYMP_ cg0235 LOC285550 NM_0011 0.04 0.02 0.07 0.03 0.07 0.89 nm42 3916 45191 LYMP_ cg2350 — — 0.12 0.08 0.06 0.04 0.05 0.91 nm43 6143 LYMP_ cg1308 ECE1 NM_0011 0.06 0.07 0.04 0.05 0.09 0.88 nm44 6983 13348 LYMP_ cg1224 KSR1 NM_0142 0.08 0.05 0.04 0.04 0.08 0.86 nm45 9234 38 LYMP_ cg1338 PHLPP1 NM_1944 0.12 0.08 0.06 0.06 0.14 0.83 nm46 1110 49 LYMP_ cg0199 SNX29 NM_0010 0.01 0.03 0.02 0.01 0.03 0.38 nm47 0910 80530 LYMP_ cg2510 H6PD NM_0042 0.04 0.04 0.02 0.02 0.05 0.76 nm48 3337 85 CD4+ CD4+ CD8 + CD4 + Th Th Cyto- Marker- Th CD4 + CD4 + Central Effect. toxic NK ID B-Cells naive Th1 Th2 Mem. Mem. T-Cells T-Cells Discovery Fragment LYMP_ 0.04 0.11 0.02 0.02 0.02 0.03 0.04 0.03 AGAGGAAGCGGC nm1 AGTGGCAGCGTGG CAGGCAGCGGGCG GGTTCTAGGTCG LYMP_ 0.06 0.10 0.02 0.03 0.02 0.06 0.03 0.05 CGTGCCTTCTCGC nm2 GCTCCGATCACCT GGCGCTGCACATG AAACGGCACAT LYMP_ 0.05 0.05 0.03 0.03 0.03 0.03 0.02 0.02 TCAGAACAGTGCG nm3 GGCTAGAGGCGCA CACGTTTCATCTA GGCTTCGGGCG LYMP_ 0.12 0.17 0.10 0.11 0.13 0.12 0.17 0.08 ATAAAAGCAACCC nm4 AGGGAGCTATTTG GTGGCTTCTGGCT TCTGACTGCCG LYMP_ 0.05 0.09 0.11 0.08 0.10 0.15 0.05 0.09 GGTGCTCACTGGC nm5 TCCAGACGTGGAT CTGCAGCTGGGAA TCAAGTGATCG LYMP_ 0.13 0.08 0.06 0.06 0.07 0.08 0.07 0.07 TTTCCCAGTCAGC nm6 AGGATGGGCACTG CAGATGTGTGTCT GCATGCCAGCG LYMP_ 0.17 0.03 0.01 0.03 0.03 0.03 0.04 0.02 CGGGCTCTCACAC nm7 GTGGGCCACCATC CGCCTGCCCCAGT CACCCCGGGGC LYMP_ 0.14 0.09 0.05 0.05 0.05 0.07 0.05 0.06 CGCAGGCAGGTAG nm8 AGGTCCCAAGTCT ATTCAGGGCCTCA TTTGTGACTGA LYMP_ 0.04 0.04 0.02 0.03 0.02 0.03 0.04 0.07 AGAAAGCACCACA nm9 GGTAATAAAAACA CCTAAAAAGGTCA GCAGAAACTCG LYMP_ 0.97 0.95 0.97 0.96 0.98 0.96 0.96 0.97 CGCAACCCCCAGT nm10 GACACAACCCCCA GTGACGCAACCCC GCCACCCAATG LYMP_ 0.95 0.94 0.96 0.96 0.95 0.95 0.97 0.96 CGAGGAGCGGGCG nm11 TGCTGCGCTGCTT CTCTTTGAGTCATC TGGGTCCTCG LYMP_ 0.86 0.95 0.93 0.92 0.94 0.93 0.96 0.93 CGACAATGTAAGC nm12 CTCGCCCCCTGCC TGTTGCTCTCGTCC CCACGGCCTG LYMP_ 0.95 0.95 0.94 0.95 0.93 0.95 0.96 0.87 CGGCCACGGCGGG nm13 CACTCAGCATTTC CTGATGACAGAAC AGTGCCGTTGG LYMP_ 0.96 0.95 0.96 0.96 0.97 0.95 0.97 0.97 CGCAAAAGCCTTG nm14 CAACACACAACAG CACAGACAAACCC CCCAGACACGG LYMP_ 0.91 0.90 0.91 0.90 0.89 0.89 0.92 0.90 ATTTCGAAATAAA nm15 GGAGCTTGCATGA ATGACGATTTCCA AACTTCTCTCG LYMP_ 0.97 0.96 0.96 0.97 0.98 0.96 0.97 0.95 CCTGCGCTCTGAC nm16 ACCAGCCGTGTAA GGGCACAGACTCG GCTGCTGTTCG LYMP_ 0.97 0.96 0.96 0.96 0.97 0.96 0.96 0.93 CGTTCAGATCTGT nm17 TGCGACTCTTCAG ATCACTTCCCGTTT TGCAATCACG LYMP_ 0.86 0.90 0.92 0.91 0.92 0.93 0.93 0.92 CACATCCTGCCCC nm18 CTGAGCAGTGGAG AGCCACACGTGTG GAAATCTTGCG LYMP_ 0.97 0.96 0.96 0.96 0.97 0.96 0.97 0.96 CGCCCACTTTGCC nm19 GGTGGGACAGAGT GGCTGACGGCGTG TGGCACAGGCG LYMP_ 0.95 0.96 0.97 0.98 0.97 0.96 0.98 0.97 CGCACTAACGTGA nm20 ATGCCGCATGTAC AGATGACCACAGT GCTCGGAGGGT LYMP_ 0.43 0.89 0.97 0.97 0.98 0.96 0.97 0.97 GAGTGGCAGAGGC nm2l GAGAACGGATCGC TGGAGGCCCGACG TCTCGTTCACG LYMP_ 0.83 0.93 0.95 0.95 0.94 0.94 0.96 0.94 ATATTTAAGGCAT nm22 CGCCCCTCAGGGA GCCGAGCACTGAT TTCCACAGCCG LYMP_ 0.62 0.83 0.89 0.92 0.90 0.92 0.92 0.93 CGTGCGTGCTCCA nm23 TCTCCCGCAGCCG AGCCGCCCATTGC TCATCTTTTGC LYMP_ 0.87 0.90 0.89 0.88 0.90 0.90 0.94 0.91 AGCGGGTAAGTAA nm24 TGCATTCAAGGTT GCACAACTAGTAA ATGCTTCATCG LYMP_ 0.93 0.92 0.90 0.91 0.91 0.92 0.93 0.87 CGTGGGATCCCAT nm25 GCCACCTTCCTGC CAAATGACCATGT GTAAATTGCTT LYMP_ 0.91 0.91 0.91 0.91 0.91 0.92 0.92 0.92 CGAACCAGGAACT nm26 CTCTTATTCCATGG ACTGTGGTCTGGG TCAGTAGGCT LYMP_ 0.88 0.88 0.89 0.89 0.89 0.90 0.90 0.87 CGGCTTCTTTAATT nm27 GTGCAATCTGTGT CAGTGGGGAAGCA CAAATAGGAT LYMP_ 0.91 0.91 0.90 0.90 0.91 0.90 0.92 0.90 CGGAGATTGCCCA nm28 ACCAAAGAGCAGA AGTTCACAGAATA TCTCTTCTTGG LYMP_ 0.88 0.85 0.94 0.93 0.92 0.93 0.92 0.96 CGGGCTCCACCAC nm29 GAAGCGCAGCTTG CCATCTGCGAGCT GCTCCAGCGCG LYMP_ 0.84 0.90 0.92 0.92 0.94 0.91 0.93 0.92 GTATTTGTTACAG nm30 CAGTACCCTATTC CCCGTACCAAAAA TCTGTGTTACG LYMP_ 0.86 0.91 0.85 0.85 0.88 0.86 0.90 0.90 AATGATGAAATCC nm31 AGCCATTCTGACA CTGTTCCTTATCTA GGATCTCTCG LYMP_ 0.89 0.92 0.92 0.91 0.93 0.91 0.92 0.94 GAGTCTGGAGAGA nm32 GCAATGTCTCCAT GGAGCGGGTGCCT GGCTGTGGTCG LYMP_ 0.93 0.92 0.87 0.88 0.90 0.89 0.89 0.84 CGGCGAATCTCAT nm33 CAAACTTTGAGAA AAAAAAACAGCTC ATCACAGAGAT LYMP_ 0.88 0.88 0.90 0.89 0.89 0.90 0.89 0.88 CGCCAGCAAGGTG nm34 CATGATCGTCCAC CAGGGCACCATTC TGGATAATGTT LYMP_ 0.93 0.91 0.91 0.89 0.90 0.89 0.92 0.91 CGGATGAGGTCTG nm35 CAGTTGCCCCACC TTACTATCTTGAG AGTTCCCAGGG LYMP_ 0.92 0.91 0.92 0.92 0.93 0.94 0.93 0.91 ACGAATTTAAGCT nm36 TTATGCCACAATT TCCCAATTCAACA TAAAGCTAACG LYMP_ 0.86 0.90 0.90 0.91 0.90 0.91 0.91 0.91 GTTTTGTTTCCTCA nm37 TACCTTACATTGT GAAATACAAAATT AGCTAATGCG LYMP_ 0.95 0.94 0.97 0.96 0.96 0.97 0.97 0.97 CGCGACGCGCTCA nm38 TCTGCCACCCACA CGAAGACAAAACA CAATGGTTATG LYMP_ 0.88 0.88 0.88 0.86 0.87 0.88 0.89 0.87 CAGAGGCCAGAGA nm39 CTTGAATTTACAA GGAGGGTCCTCAA CACAGACATCG LYMP_ 0.87 0.90 0.91 0.91 0.90 0.91 0.92 0.90 ACCCTGGTATTTC nm40 ATCACTTTCTTGCC TAACTTAGCAGAA ACATGTATCG LYMP_ 0.90 0.89 0.91 0.89 0.90 0.90 0.91 0.91 GTTACACTATAAA nm41 TAGATGTTCACTG ACCAAATACTCCT ACTAGTTCTCG LYMP_ 0.85 0.85 0.89 0.88 0.86 0.90 0.88 0.85 CGGCATTGATGTT nm42 GCTTCACGTTGCT GATGCTTAAGCAA TGTATATTGTG LYMP_ 0.89 0.85 0.86 0.88 0.90 0.86 0.92 0.90 CGTCGTTTTAAA nm43 ATGTGCTATCATTT CCTTGTTATAGTTG TGCAAGATT LYMP_ 0.83 0.88 0.90 0.90 0.90 0.90 0.90 0.89 TGGCTCCAGTTTC nm44 CAAGTGACGCAAC CAAGTGTCTGGAT TCAGAGAATCG LYMP_ 0.86 0.88 0.87 0.89 0.87 0.89 0.90 0.86 ACAAATGTAAAAG nm45 CCTGGCAGCTTCC CCAGGAGAGTGCG GGTATGGGCCG LYMP_ 0.89 0.90 0.93 0.93 0.91 0.92 0.94 0.94 CATAGTGCTCGTGT nm46 CGTAATAATCTGG CAGCTGGTCCAGC TGGTAGTGCCG LYMP_ 0.59 0.88 0.96 0.97 0.96 0.96 0.93 0.94 CGCCGGCCAAATG nm47 CAACCAGCAGAGA TATGACCCCGACC CGTCTAAAGCC LYMP_ 0.73 0.87 0.89 0.90 0.88 0.89 0.89 0.88 TGGGGCCAACAGG nm48 CATGATTACCACA

In table 4, regions that contain CpGs that are specific for the blood cell types granulocytes, monocytes, CD4+ cells, cytotoxic T-cells, B-cells, Natural Killer-cells, and Natural Killer T-cells are listed, as well as their SEQ ID NOs for the so-called “discovery fragment” (preferred region) and the discriminative “region of interest” (more preferred region). The discovery fragments comprise at least one CpG that is specific for the cell type as indicated, and thus suitable to distinguish this cell type from all other cell types of the haemogram. The discriminative region of interest (ROT) sequences are regions that are positioned around the discovery region, and which form the basis for the design of the specific assay for a specific cell type as indicated, and contain additional relevant CpGs, that is, a sequence of CpGs that can also be used in order to distinguish between the call types as indicated.

In table 4A to 4J, regions that contain CpGs that are specific for the respective blood cell types as shown in each table header are listed. The sequence provided in the column “discovery fragment” is the preferred region and comprises at least one CpG that is specific for the cell type of the respective table (identifiable by the shown data). Also comprised in the context of the various embodiments and aspects of the invention is a region 500 base pairs upstream and downstream of (therefore “around”) the sequence of the “discovery fragment” in the human genome for each marker. The region 500 base pairs upstream and downstream of the “discovery fragment” are the discriminative ROI of the marker of the tables 4A to 4J.

The present invention therefore also pertains to a bisulfite conversion of at least one CpG position within any one of the “discovery fragments” or ROI (500 bp up and downstream for each “discovery fragment” in the human genome) of any one of the Tables 4 and 4A to 4J as shown above, which is indicative for a respective cell type as listed in the tables 4. The T-lymphocytogram in all of the embodiments and aspects of the invention may therefore contain any of the cell types listed in the above tables 4 and 4A to 4J, and any combinations of these cell types.

An additional region for neutrophilic granulocytes (nGRC) is derived from the Lipocalin-2, neutrophil gelatinase-associated lipocalin (LCN2) genomic region (Ensembl-ID: ENSG00000148346); herein designated AMP1730. The AMP 1730 genomic sequence and the discriminative ROI 1132 are SEQ ID NOs: 686 and 685 respectively. See also FIG. 2.

Additional regions for eosinophilic granulocytes (eGRC) arc derived from the proteoglycan 2 (PRG2) genomic region (Ensembl-ID: ENSG00000186652), herein designated as AMP 2034 and 2035, respectively. The AMP 2034 and 2035 genomic sequences, and the discriminative ROI1403 are SEQ ID NOs: 687, 688, and 689, respectively. See also FIG. 3.

Preferably, the cell-specific gene regions as described herein are selected to discriminate one cell type or subpopulation of cells from all other cell types, such as the leukocytogram, T-lymphocytogram, granulocytogram, monocytogram, B-lymphocytogram and/or NK cytogram as described herein. Thus, highly specific cell-type markers are used as a basis for identification and quantification that are not based on protein expression levels but on cell type-specific epigenetic information. The method provides a clear yes/no information and is independent of thresholding as the cell-specific CpG-rich genomic region is bisulfite convertible or not, is detectable by qPCR or not as well as genomic copies do not vary. The method also detects and identifies as well as quantifies a potentially unlimited number of subpopulations of cells, and the detection limit for, for example, regulatory T cells is at 0.3%.

Preferred is a method according to the present invention, wherein the cells that are detected and thus for the epigenetic haemogram are selected from a leukocytogram, and/or a T-lymphocytogram, and/or a granulocytogram, and/or a monocytogram, and/or a B-lymphocytogram, and/or a NK cytogram.

Preferably, said marker regions as analyzed are specific for the cells of a pre-selected haemogram, and these cells are preferably selected from T-lymphocytes, natural killer cells, B-lymphocytes, monocytes, granulocytes, and combinations thereof, for a leukocytogram, selected from CD3⁺CD4⁺, CD4₊ memory, CD4⁺ effector cells, CD4⁺ naïve, CD3⁺CD8⁺, CD8 positive, CD8⁺ memory, CD8⁺ effector cells, CD8⁺ naïve, CD3⁺CD8⁻CD4⁻, CD3⁺CD8⁺CD4⁺, NKT cells, iTreg, Treg, Tfh, Th1, Th2, TH9, Th17, Th19, Th21, Th22, memory and effector T helper cells, and combinations thereof, for a T-lymphocytogram, selected from basophilic, eosinophilic, neutrophilic granulocytes, and/or granulocytic myeloid-derived suppressor cells, and combinations thereof, for a granulocytogram, selected from CD14⁺ monocytes, CD14⁻ monocytes, macrophages, plasmacytoid dendritic cells, myeloid-dendritic cells, intermediate monocytes, classical monocytes, non-classical monocytes, and/or overall dendritic cells, and combinations thereof, for a monocytogram, selected from naïve B cells, pre B cells, memory B cells, transitional B cells and/or immature B cells, and combinations thereof, for a B cell cytogram, and selected from CD56^(dim) and/or CD56^(bright) NK cells for an NK cytogram.

In contrast to the term “cell-specific regions”, the term “cell-unspecific regions” herein shall mean genetic regions in the genome of cells and/or nucleic acids that are selected to be unspecific, i.e. arc specific for more than one, preferably all, cell type and/or subpopulation of cells. These cell-unspecific regions also include the genes of certain markers (such as, for example, certain protein markers), such as 5′ untranslated regions, promoter regions, introns, exons, intron/exon borders, 3′ regions, CpG islands, and in particular include specific regions as amplified after bisulfite treatment (amplicons) that are “informative” for more than one cell type and/or subpopulation of cells. Examples for these cell-unspecific regions are known from the literature, and are selected from, for example regions comprising a housekeeping gene, such as GAPDH, ACTB (beta-actin), UBC (ubiquitin C), ribosomal proteins (e.g. RPS27A, RPS20, RPL11, RPL38, RPL7, RPS11, RPL26L1), CALR (calreticulin), ACTG1 (gamma actin) RPS20 (ribosomal protein S20), HNRPD (ribonucleoprotein D), NACA (nascent poly-peptide-associated complex subunit alpha), NONO (octamer-binding protein), PTMAP7 (prothymosin), GFRA4 (GDNF receptor alpha-4), CDC42 (GTP-binding protein), EIF3H (translation initiation factor), UBE2D3 (ubiquitin-conjugating enzyme), and genes as described in, for example, She et al. (Definition, conservation and epigenetics of housekeeping and tissue-enriched genes. BMC Genomics. 2009 Jun. 17; 10:269.), and PCT/EP2011/051601.

The method according to the present invention generally identifies the quantitative cellular composition of a biological sample. Preferred is a method according to the present invention, wherein said biological sample is a sample of unknown cellular composition. Nevertheless, also samples of known cellular composition, or even partially known composition can be quantified.

Biological samples to be analyzed can be stored fresh-frozen, paraffin-embedded or Heparin, Citrate or EDTA-stabilized as cells in samples do not need to be intact. The present method is very robust and allows, in contrast to flow cytometry, a parallel, independent assessment of cell identity and quantity as well as sample composition. A very good correlation to FACS is provided, too.

The biological sample to be analyzed can be any sample comprising one or more type(s) of cells or that is suspected of comprising one or more type(s) of cells that are to be quantified. Preferred materials/biological samples are selected from a blood sample, in particular peripheral, capillary or venous blood samples, blood clots, or samples that are considered to contain blood cells as e.g. synovial fluid, lymph fluid, sputum, urine, tumor samples, as well as other fluid and tissue samples, histological preparations, DBS, artificially generated cells and mixtures thereof (e.g. cell culture samples).

Yet another aspect of the present invention then relates to a method according to the present invention, further comprising the step of concluding on the immune status of a mammal based on said epigenetic haemogram as produced.

Yet another aspect of the present invention then relates to a method according to the present invention, further comprising the step of monitoring said cellular composition in said biological sample as identified by comparing said composition and/or haemogram as identified with the composition in an earlier biological sample taken from the same mammal, and/or with the composition in a control sample. In this aspect, for example, modifications and changes of the cellular composition in a patient can be monitored during a medical treatment.

Yet another aspect of the present invention then relates to a method for diagnosing a disease or a predisposition for a disease, comprising a method according to the present invention as described above, and the step of concluding on the disease or a predisposition for said disease based on the cellular composition in said biological sample as identified. In this aspect, for example, modifications and changes of the cellular composition in a patient can be used for diagnosing a disease or a predisposition for a disease, in particular when the sample is compared to a sample of a healthy subject or to medical reference ranges. Preferably, said biological sample is a blood sample, in particular a whole or peripheral blood sample, and said cell-specific regions in the genome of cells in said sample are selected from regions specific for blood cell types. The disease to be diagnosed can be selected from the group consisting of immune diseases or conditions, transplant rejections, infection diseases, cancer, neurological diseases, allergy, primary and secondary immune deficiencies and hematologic malignancies such as, for example, lymphatic neoplasms, mature B-cell neoplasms, mature T- and NK-cell neoplasms, Hodgkin lymphomas, lympho-proliferative processes after transplantations, HIV and AIDS, Graft versus Host disease, rheumatoid arthritis, lupus erythematosus, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, leukemia/lymphoma, lung cancer, prostate cancer, uterine cancer, skin cancer, endocrine cancer, kidney cancer, urinary cancer, pancreatic cancer, other gastrointestinal cancers, ovarian cancer, cervical cancer, head and neck cancer, adenomas, birth defects, myopathies, mental retardation, obesity, diabetes, gestational diabetes, multiple sclerosis, and asthma.

In one preferred embodiment of the present invention, the diagnostic use of the epigenetic haemogram is also based on the use of ratios of different populations and/or/to different subpopulations (subhaemograms) and/or/to of cells belonging to one subhaemogram according to the said epigenetic haemogram. Such ratios are e.g. but are not limited to, population of regulatory T cells in relation to CD3⁺ T-lymphocytes, or regulatory T cells in relation to population of CD4⁺ T-lymphocytes, or regulatory T cells in relation to population of CD8⁺ T-lymphocytes, or CD3⁺ T-lymphocytes to CD4⁺ T-helper cells, or CD3⁺ T-lymphocytes to CD8⁺ cytotoxic T cells, or CD4⁺ T-helper cells to CD8⁺ cytotoxic T-cells, or Th1 to Th2, or Th1 to Th17, or Th2 to Th17, or memory or naïve CD4⁺ T-helper cells to CD3⁺ T-lymphocytes, or memory CD8⁺ cytotoxic T-cells to CD3⁺ T-lymphocytes, all as subpopulations of the T-lymphocytogram; or CD3⁺ T-lymphocytes related to neutrophilic granulocytes, or macrophages to CD4⁺ T-helper cells; CD4⁺ T-lymphocytes related to neutrophilic granulocytes, or CD8⁺ T-lymphocytes related to neutrophilic granulocytes all as relations between cells of different subhaemograms; or CD3⁺ T-lymphocytes related to granulocytes, or B-lymphocytes to CD3⁺ T-lymphocytes, or monocytes to CD3⁺ T-lymphocytes, or monocytes to B-lymphocytes all as ratios out of populations of the leukocytogram; or CD3⁺ T-lymphocytes or monocytes or B-lymphocytes, or granulocytes or NK cells related to overall leukocytes. But also other ratios of subpopulations assessed according to the present invention and according to the epigenetic haemogram can be used as a diagnostic method. The disease can be selected from the group consisting of immune diseases or conditions, transplant rejections, infection diseases, cancer, neurological diseases, allergy, primary and secondary immune deficiencies and hematologic malignancies such as, for example, lymphatic neoplasms, mature B-cell neoplasms; mature T- and NK-cell neoplasms, Hodgkin lymphomas, lympho-proliferative processes after transplantations, HIV and AIDS, Graft versus Host disease, rheumatoid arthritis, lupus erythematosus, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, leukemia/lymphoma, lung cancer, prostate cancer, uterine cancer, skin cancer, endocrine cancer, kidney cancer, urinary cancer, pancreatic cancer, other gastrointestinal cancers, ovarian cancer, cervical cancer, head and neck cancer, adenomas, birth defects, myopathies, mental retardation, obesity, diabetes, gestational diabetes, multiple sclerosis, and asthma. The diagnostic use encompasses but is not limited to the diagnosis of a disease and/or the follow-up of a disease and/or the predisposition for a disease and/or the monitoring of an effect of a chemical or biological substance.

The epigenetic haemogram of the invention is in another embodiment used for the assessment of the risk to develop a disease in a patient, therefore for diagnostic purposes. In one preferred embodiment of the present invention, the use of the epigenetic haemogram for the assessment of the risk to develop a disease is also based on the use of ratios of different populations and/or/to different subpopulations (subhaemograms) and/or/to of cells belonging to one subhaemogram according to the said epigenetic haemogram. Such ratios are e.g. but are not limited to, population of regulatory T cells in relation to CD3⁺ T-lymphocytes, or regulatory T cells in relation to population of CD4⁺ T-lymphocytes, or regulatory T cells in relation to population of CD8⁺ T-lymphocytes, or CD3⁺ T-lymphocytes to CD4⁺ T-helper cells, or CD3⁺ T-lymphocytes to CD8⁺ cytotoxic T cells, or CD4⁺ T-helper cells to CD8⁺ cytotoxic T-cells, or Th1 to Th2, or Th1 to Th17, or Th2 to Th17, or memory or naïve CD4⁺ T-helper cells to CD3⁺ T-lymphocytes, or memory CD8⁺ cytotoxic T-cells to CD3⁺ T-lymphocytes, all as subpopulations of the T-lymphocytogram; or CD3⁺ T-lymphocytes related to neutrophilic granulocytes, or macrophages to CD4⁺ T-helper cells; CD4⁺ T-lymphocytes related to neutrophilic granulocytes, or CD8⁺ T-lymphocytes related to neutrophilic granulocytes all as relations between cells of different subhaemograms; or CD3⁺ T-lymphocytes related to granulocytes, or B-lymphocytes to CD3⁺ T-lymphocytes, or monocytes to CD3⁺ T-lymphocytes, or monocytes to B-lymphocytes all as ratios out of populations of the leukocytogram; or CD3⁺ T-lymphocytes or monocytes or B-lymphocytes, or granulocytes or NK cells related to overall leukocytes.

But also other ratios of subpopulations as assessed in accordance with the present invention and according to the epigenetic haemogram can be used to assess the risk for developing a disease. The disease for the herein described embodiment can be selected from the group consisting of immune diseases or conditions, transplant rejections, infection diseases, cancer, neurological diseases, allergy, primary and secondary immune deficiencies and hematologic malignancies such as, for example, lymphatic neoplasms, mature B-cell neoplasms, mature T- and NK-cell neoplasms, Hodgkin lymphomas, lympho-proliferative processes after transplantations, HIV and AIDS, Graft versus Host disease, rheumatoid arthritis, lupus erythematosus, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, leukemia/lymphoma, lung cancer, prostate cancer, uterine cancer, skin cancer, endocrine cancer, kidney cancer, urinary cancer, pancreatic cancer, other gastrointestinal cancers, ovarian cancer, cervical cancer, head and neck cancer, adenomas, birth defects, myopathies, mental retardation, obesity, diabetes, gestational diabetes, multiple sclerosis, and asthma. The diagnostic use encompasses but is not limited to the diagnosis of a disease and/or the follow-up of a disease and/or the predisposition and/or the assessment of a risk for a disease and/or the monitoring of an effect of a chemical or biological substance.

As indicated, the above mentioned ratios as assessed in accordance with the present invention bear the potential to indicate e.g. the risk to develop a certain disease during the life time of a subject. A clinical role in risk assessment was found for the ratio of regulatory T-lymphocytes to CD3+T-lymphocytes. Particularly preferred in the context of the present invention is that an increase in the ratio of regulatory T-lymphocytes to CD3+T-lymphocytes indicates a risk to develop cancer (cancerous disease) during life time. The cancer is selected from but not limited to the list as provided herein above, wherein a high impact of an increased ratio of regulatory T-lymphocytes to CD3+T-lymphocytes is expected for the development of lung cancer, which is particularly preferred. Furthermore, ratios bear the potential to predict the development of Graft versus Host Disease wherein an increased ratio of regulatory T-lymphocytes to CD4+T-lymphocytes within the first two weeks after stem cell transplantation predicts the development of a graft versus host disease.

Yet another aspect of the present invention then relates to a method for identifying the effect of a chemical or biological substance or drug on the composition of cells, comprising performing the method according to the present invention as described above, preferably on a blood sample obtained from a mammal treated with or exposed to said substance, and comparing the composition of cells in said sample with the composition of samples before treatment or with the composition of an untreated sample. The mammal to be treated with said chemical or biological substance or drug might be healthy or suffers from a disease selected from the group consisting of immune diseases or conditions, transplant rejections, infection diseases, cancer, neurological diseases, allergy, primary and secondary immune deficiencies and hematologic malignancies such as, for example, lymphatic neoplasms, mature B-cell neoplasms, mature T- and NK-cell neoplasms, Hodgkin lymphomas, lympho-proliferative processes after transplantations, HIV and AIDS, Graft versus Host disease, rheumatoid arthritis, lupus erythematosus, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, leukemia/lymphoma, lung cancer, prostate cancer, uterine cancer, skin cancer, endocrine cancer, kidney cancer, urinary cancer, pancreatic cancer, other gastrointestinal cancers, ovarian cancer, cervical cancer, head and neck cancer, adenomas, birth defects, myopathies, mental retardation, obesity, diabetes, gestational diabetes, multiple sclerosis, and asthma.

Yet another aspect of the present invention then relates to a diagnostic kit and its use, comprising materials for performing the method according to the invention as described herein, optionally with instructions for use. The diagnostic kit particularly contains oligonucleotides (e.g. for producing amplicons) specific for regions of interest, bisulfite reagents, and/or components for PCR. The diagnostic kit and its use encompasses but is not limited to the diagnosis of a disease and/or the follow-up of a disease and/or the predisposition and/or the assessment of a risk for a disease and/or the monitoring of an effect of a chemical or biological substance.

As mentioned above, currently, in both, clinical diagnostics and research, and drug development, a new method to provide a precise and comprehensive quantification of leukocytes and their subpopulations is desired even if biological samples are not intact anymore. The present invention, overcomes most problems of current, routinely used quantitative methods, flow cytometry and immune histochemistry, but more importantly, overcomes several biochemical and technical problems of qPCR in regard to absolute quantification of target cells. The present invention thus provides a method to effectively detect and quantify the different cell populations. In particular, the present method for the first time allows for an expression-independent method for the assessment of a comprehensive blood cell picture. Moreover, the present invention enables flexible time framing which is not dependent on quick sample processing but rather allows long term sample storage and individual coordination between sample collecting and sample processing.

The present invention will now be explained further in the following examples and figures, nevertheless, without being limited thereto. For the purposes of the present invention, all references as cited herein are incorporated by reference in their entireties.

FIG. 1 shows a schematic overview over the epigenetic haemogram. The haemogram comprises the leukocytogram, which includes B cells, monocytes, granulocytes, CD3⁺ T-lymphocytes, and NK cells. Each subpopulation establishes an additional cytogram, respectively i.e. the B-lymphocytogram, monocytogram, granulocytogram, T-lymphocytogram, and NK cytogram. For these five sub-cytograms, the corresponding cell types are depicted. Each of these five sub-cytograms can be divided into additional subpopulations, e.g., the T cell cytogram can be further divided into the CD4⁺ T-helper cytogram and the CD8⁺ cytotoxogram.

FIG. 2 shows a matrix indicating bisulfite-non-convertibility in cell-type specific genomic marker region. Different cell types were analyzed indicating that CpGs within genomic region AMP1730 are completely convertible by bisulfite treatment corresponding to 0% bisulfite-non-convertibility. The total fraction of granulocytes corresponds to neutrophilic granulocytes. Neutrophilic granulocytes account for about 90% of granulocytes, eosinophilic for about 7%, and basophilic for about 3% (see Example 4)

FIG. 3 shows a matrix indicating bisulfite-non-convertibility in cell-type specific genomic marker regions. Different cell types were analyzed indicating that CpGs within genomic region AMP2034 and 2035 are, in contrary to other cell types given, convertible by bisulfite to a high extent and indicative for this specific cell-type (see Example 5).

FIG. 4 shows the results of the test-template as amplified according to Example 7. unM (TpG Template): bisulfite-converted test-DNA; Meth (CpG template): non-bisulfite converted test-DNA; NTC: no template control; left panel: Mg2+ concentration 3.2 mM; right panel: Mg2+ concentration 3.6 mM.

SEQ ID No. 1 to 689 show sequences as used in the context of the present invention.

EXAMPLES

The present examples have been performed on a sample of known and unknown leukocyte and T-lymphocyte compositions. The person of skill will understand how to modify the experiments in order to identify and quantify other cell types, in particular blood cells in the context of an epigenetic haemogram, without undue burden and/or the need to become inventive.

Example 1 Assessment of Cell-Specific Assay-Correction Factors Using a Sample of Known Composition

The inventors provided a human blood sample of known leukocyte and T-lymphocyte composition. The composition of this blood sample was analyzed via flow cytometry. The sample contained 61% granulocytes, 12% monocytes, 3% B-lymphocyte, 4% natural killer cells, and 19% T-lymphocytes (Table 5). The T cell population consisted of 13% of CD4⁺ T helper cells, 1.4% regulatory T cells, 5% CD8⁺ cytotoxic cells, and 2% naïve CD8⁺ cells.

In a next step, this sample of known leukocyte and T-lymphocyte composition was analyzed for the relative amount of bisulfite convertible chromatin in cell-type specific gene regions, resulting in a unique, discriminating cell-type specific pattern of bisulfite convertible chromatin, e.g. for granulocytes a region in the gene for neutrophil gelatinase-associated lipocalin, for monocytes a region in the leukocyte immunoglobulin-like receptor gene, for B cells in a region of the gene for the low-affinity receptor for IgE, for natural killer cells a region in the gene for oxysterol-binding protein-like protein 5 isoform a, for T-lymphocytesin a region in the CD3D/G gene, for CD4⁺ T helper cells in a region in the CD4 gene, for regulatory T cells in a region in the FOXP3 gene, for CD8⁺ cytotoxic T cells in a region in the CD8A/B gene, for naïve CD8⁺ cells a region in the endosialin gene. Analyses were performed by qPCR using a bisulfite-converted normalization standard indicating the relative amount of numbers of gene copies containing mentioned unique, said cell-type specific pattern of bisulfite convertibility. These relative numbers of cell-specific gene copies indicate the relative amount of said specific cells.

This relative number of specific cells (said leukocytes and T-lymphocytes) was compared with the result of flow cytometry. Both results were set in relation, and a correction factor was determined (Table 1). Flow cytometry revealed 61% and qPCR 91.6% of granulocytes, and therefore the cell-specific granulocyte assay-correction factor was 1.502.

Correction factors were determined separately for each set of assessments as well as are incorporated into data base for assay-specific correction factors. In addition to the individual and separate determination of correction factors (for each set of assessments), the average of past correction factors can be used as well.

TABLE 5 Assessment of cell-specific assay-correction factors. Cell composition of human blood sample was assessed by flow cytometry and qPCR for leukocytes as well as T-lymphocytes. qPCR was performed using a bisulfite-converted normalizations standard. Correction factors for following qPCRs on samples of unknown composition were determined by ratio of qPCR/FC. (C-Factor) correction factor, (FC) Flow cytometry, (GRK01) internal sample number. (qPCR) real time quantitative polymerase chain reaction. FC GRK01 qPCR (%) GRK01 C-Factor Leukocytogram granulozytes 61.0 91.6 1.502 monozytes 12.0 29.9 2.494 B cells 3.0 1.3 0.429 natural killer cells 4.0 3.9 0.977 T cells 19.0 29.8 1.568 T-Lymphocytogram CD4⁺ T helper cells 13.0 9.7 0.745 regulatory T cells 1.4. 2.3 1.668 CD8⁺ cytotoxix T cells 5.0 8.0 1.594 naive CD8⁺ cells 2.0 2.1 1.051

Example 2 Assessment of Absolute Cell Composition in an Unknown Blood Sample of Healthy Volunteers Using an Assay-Correction Factor Determined Using a Sample of Known Composition (as Shown in Example 1)

Human blood samples of unknown leukocyte and T-lymphocyte composition of healthy volunteers were obtained for assessment of absolute leukocyte and T-lymphocyte composition via qPCR. As for Example 1, DNA of blood samples were isolated, bisulfite converted and relative amount of bisulfite converted DNA assessed via qPCR under the use of Bisulfite-converted normalization standards. Amount of bisulfite convertible DNA in cell-specific gene regions was set in relation to bisulfite-convertible DNA of cell-unspecific DNA region (always, cell independent, constant pattern of bisulfite-convertibility) to obtain relative amount of assessed cells.

Cell-specific assay-correction factors were determined in a parallel experimental set for assays of granulocytes, monocytes, B-lymphocytes, natural killer cells, T-lymphocytes, CD4⁺ T helper cells, regulatory T cells, and CD8⁺ cytotoxic T cells using flow cytometry on a human blood sample (methodology see example 1, human blood sample differs for Example 2 compared to Example 1). Relative amounts of assessed cells as obtained were corrected using the cell-specific assay correction factors. E.g., qPCR for monocytes patient sample S04 gave a relative amount of monocytes of 7.94%, but the correction revealed an absolute cell amount of 3.69% monocytes.

One would expect the sum of cells belonging to a leukocytogram to be 100%, and the sum of cells belonging to a T-lymphocytogram to have exactly the same amount of cells as determined for T-lymphocytes in the leukocytogram. It is known that even the flow cytometry quantification is not without limitations, as described above.

Flow cytometry measurement errors are reflected in qPCR corrections. On the other hand, the epigenetics based qPCR, as described herein, detected cell types independently of marker expression. Even if a cell-specific marker is expressed at a very low amount, or is not present at all, epigenetic-qPCR can detect these cells (e.g. as found for Th17 cells, see above). In addition, certain cells do express cell-specific markers, even if these cells did not enter a specific cellular state known to be associated with the marker expression (e.g. as found for regulatory T cells, see description above). Such cells are not detected by epigenetic-based qPCR. Additionally, for this example, the selection of T-lymphocytes (CD4⁺ T helper cells, CD8⁺ cytotoxic cells) does not represent the complete T-lymphocyte set (see FIG. 1). Cytograms represent the current status of scientific knowledge and cannot exclude the existence of additional cell types or of the incorrect definition of subpopulations thereof.

TABLE 6 Assessment of absolute cell composition of blood from healthy volunteers. Cell composition of human blood samples were assessed by qPCR for leukocytes as well as T-lymphocytes. qPCR was performed using a bisulfite-converted normalizations standard. Correction factors for qPCRs were determined in a parallel set of experiments (not described in detail here, example of assessment of C-Factor see Example 1). (C-Factor) correction factor, (FC) Flow cytometry, (S04)(S08) internal sample numbers. (qPCR) real time quantitative polymerase chain reaction. Leukocytogram (% relative cell amount) qPCR-S04 qPCR-S08 granulozytes 79.74 81.29 monozytes 7.94 11.05 B cells 1.63 1.68 natural killer cells 2.74 2.04 T cells 23.25 22.09

Leukocytogram (% absolute cell amount) C-Factor qPCR-S04 qPCR-S08 granulozytes 1.23 64.74 65.99 monozytes 2.15 3.69 5.13 B cells 0.39 4.13 4.26 natural killer cells 0.97 2.88 2.11 T cells 1.54 19.27 18.31 Sum 94.71 95.8 T-Lymphocytogram (% relative cell amount) qPCR-S04 qPCR-S08 CD4⁺ T helper cells 5.89 5.11 regulatory T cells 1.67 1.15 CD8⁺ cytotoxix T cells 5.26 3.80

T-Lymphocytogram (% absolute cell amount) C-Factor qPCR-S04 qPCR-S08 CD4⁺ T helper cells 0.45 13.16 11.42 regulatory T cells 1.1 1.52 1.05 CD8⁺ cytotoxix T cells 1.09 4.85 3.5 Sum 19.53 15.97

Example 3 Assessment of Absolute Cell Composition in an Unknown Blood Sample of Auto-Immune Diseased Volunteers Using an Assay-Correction Factor Determined Using a Sample of Known Composition (as Shown in Example 1)

Human blood samples of unknown leukocyte and T-lymphocyte composition of auto-immune diseased volunteers were obtained for assessment of absolute leukocyte and T-lymphocyte composition via qPCR. As for Example 1, DNA of blood samples were isolated, bisulfite converted and relative amount of bisulfite converted DNA assessed via qPCR. Amount of bisulfite convertible DNA in cell-specific gene regions was set in relation to bisulfite convertible DNA of cell-unspecific DNA region (always, cell independent, constant pattern of bisulfite convertibility) to obtain relative amount of assessed cells.

Cell-specific assay-correction factors were determined in a parallel experimental set for assays of granulocytes, monocytes, B-lymphocytes, natural killer cells, T-lymphocytes, CD4⁺ T helper cells, regulatory T cells, and CD8⁺ cytotoxic T cells using flow cytometry on a human blood sample (methodology see example 1, human blood sample differs for Example 3 compared to Example 1). Obtained relative amounts of assessed cells were corrected using these cell-specific assay correction factors. E.g., qPCR for T-lymphocytes assessed a relative amount of T-lymphocytes of 8.49% for patient M06 and 23.94% for patient M10. Correction revealed an absolute cell amount of 5.4% and 15.3% T cells, respectively.

In comparison to data from healthy patients, see Example 2, for auto-immune diseased patient M06 an obvious decrease in 4 of the 5 subtypes of leukocytes within the leukocytogram was observed. For patient M10 an obvious decrease in absolute number of only B-lymphocytes and monocytes was observed.

Additionally, also for T-lymphocyte subtypes, differences, between both patients were observed. qPCR analysis of three subtypes of T-lymphocytes for patient M06 revealed a strong decrease of CD4+T helper cells as well as CD8+ cytotoxic cells whereas the decrease in level of regulatory T cells was less pronounced. For patient M10 all three cell levels decreased simultaneously by about 50-60% compared to the average of the two healthy patients in Example 2.

All these differences might be related to e.g. a different medication and/or disease stage of these both patients and offer a clinical routine instrument for disease diagnosis, prediction as well as accompanying monitoring.

TABLE 8 Assessment of absolute cell composition of blood from auto-immune diseased patients. Cell composition of human blood samples were assessed by qPCR for leukocytes as well as T-lymphocytes. qPCR was performed using a bisulfite-converted normalizations standard. An obvious decrease of the level of certain cell populations was seen that is known for auto immune diseases. Correction factors for qPCRs were determined in a parallel set of experiments (not described in detail here, example of assessment of C-Factor see Example 1). (C-Factor) correction factor, (FC) Flow cytometry, (S04)(S08) internal sample numbers. (qPCR) real time quantitative polymerase chain reaction. Leukocytogram (% relative cell amount) qPCR-M06 qPCR-M10 granulozytes 126.62 116.26 monozytes 3.12 3.36 B cells 0.21 0.72 natural killer cells 0.51 2.76 T cells 8.49 23.94

Leukocytogram (% absolute cell amount) C-Factor qPCR-M06 qPCR-M10 granulozytes 1.50 84.3 77.4 monozytes 2.49 1.3 1.3 B cells 0.43 0.5 1.7 natural killer cells 0.98 0.5 2.8 T cells 1.57 5.4 15.3 Sum 92.0 98.5 T-Lymphocytogram (% relative cell amount) qPCR-M06 qPCR-M10 CD4⁺ T helper cells 1.97 6.35 regulatory T cells 1.58 0.97 CD8⁺ cytotoxix T cells 2.09 3.35

T-Lymphocytogram (% absolute cell amount) C-Factor qPCR-M06 qPCR-M10 CD4⁺ T helper cells 0.7 2.6 8.5 regulatory T cells 1.7 0.9 0.6 CD8⁺ cytotoxix T cells 1.6 1.3 2.1 Sum 4.8 11.2

Example 4 Detection of Neutrophilic Granulocytes Based on AMP1730 in the Gene for Neutrophil Gelatinase-Associated Lipocalin (LCN2) (See FIG. 2)

FIG. 2 shows a matrix indicating bisulfite-unconvertibility in cell-type specific genomic marker region. Different cell types were analyzed indicating that CpGs within genomic region AMP1730 are completely convertible by bisulfite treatment corresponding to 0% bisulfite-unconvertibility. Within basophil and eosinophil granulocytes specific CpGs of AMP1730 are not convertible by bisulfite. Therefore, the term “(Total) Granulocytes” within figure corresponds to neutrophilic granulocytes. Neutrophilic granulocytes account for about 90% of granulocytes, eosinophilic for about 7%, and basophilic for about 3%.

TABLE 7 Discriminatory quality of AMP1730: qPCR using assay specific primers for AMP1730 was performed on cells indicated under “sample” to analyze amount of bisulfite-convertibility of CpGs present in genomic region given by AMP1730. DNA from purified cell samples was isolated, bisulfite treated and qPCR assay performed under the use of a bisulfite- converted normalization standard. Relative amount of cells was assessed via comparing copy numbers of busulfite-convertible DNA of AMP1730 with bisulfite-unconvertible DNA of AMP1730, named “TpG/CpG- System”. (copy numer convertible/(copy number convertible + copy number non-convertible) = % cell type). Cells were purified and sorted via flow cytometry. Within the neutrophiles cell sample, more than 95% of the cells were detected as neutrohiles using AMP1730. (bGRAN) basophiles, (eGRAN) eosinophiles (nGRAN) neutrophiles, (MOC) monocytes, (THC) CD3⁺CD4⁺ T-lymphocyets, (CTL) cytotoxic CD3⁺CD8⁺ T-lymphocytes, (NKC) CD3⁻ natural killer cells, (NKT) CD3⁺ natural killer cells, (BLC) B-lymphocytes. AMP1730 - neutrophilic granulocytes assay PCR-System specific to PCR-System specific to “TpG” “CpG” copy numbers copy numbers % nGRC CP acc. To CP acc. To ‘TpG” Sample Value plasmid units Value plasmid units variant bGRAN 35.49 14.27 29.09 875.33 1.60 eGRAN 25.24 16.20 30.68 300.00 5.12 nGRAN 30.52 270.67 35.73 11.70 95.86 MOC 35.72 12.93 29.85 525.00 2.40 THC 42.70 0.91 30.80 278.00 0.33 CTL 37.72 5.04 29.41 706.00 0.71 NKC 36.95 7.03 29.34 740.33 0.94 NKT 38.35 3.85 30.37 369.67 1.03 BLC 39.75 2.41 29.91 502.67 0.48

Example 5 Detection of Eosinophilic Granulocytes Based on AMP 2034 and/or 2035 (PRG2)

Matrix indicating bisulfite-inconvertibility in cell-type specific genomic marker regions. Different cell types were analyzed indicating that CpGs within genomic region AMP2034 and 2035 arc, in contrary to other cell types given, convertible by bisulfite to a high extent and indicative for this specific cell-type (see FIG. 3).

Example 6 Assessment of Cell-Specific Assay-Correction Factor Using a Non-Bisulfite-Converted Nucleic Acid Molecule (Plasmid Standard) as Normalization Standard

The inventors developed non-bisulfite converted, genomic plasmid standards as a normalization standard. One of these genomic plasmid standards comprises marker regions being specific for stable regulatory T cells (TSDR region)(Treg cells) as well as marker regions being cell-type unspecific (GAPDH, housekeeping gene, detecting all cells, 100% of cells). This plasmid standard is used to determine the Treg-specific assay correction factor that allows assessing the absolute amount of stable Tregs within an unknown blood sample.

In a first step, a human blood sample of unknown composition was provided, DNA isolated, and bisulfite treated. Following, the amount of bisulfite converted TSDR copies and GAPDH copies were assessed (Table 8, section 2). These qPCR analyses were performed using a bisulfite-converted normalization standard (Table 8, section 1) indicating the number of bisulfite-converted DNA copies containing the TSDR marker region as well as the GAPDH marker region (Table 8 section 2). The relative amount of stable Tregs is calculated as number of bisulfite converted TSDR copies related to bisulfite converted GAPDH copies in percent.

no. bisulfite-converted TSDR copies/no. bisulfite-converted GAPDH copies×100=% Treg

67.70/6026.67×100=1.123%

The cell-type specific region for stable regulatory T cells, TSDR, is located on the X-chromosome. For women an epigenetic silencing of one allele of the X-chromosome is known. This affect is deduced by using a factor 2 when calculating relative amount of stable Tregs (final result=2.25% stable Tregs)(Table 8, section 2).

In a second step, Treg-specific assay-correction factor based on said genomic plasmid standard was assessed. Said plasmid standard was bisulfite converted and number of plasmid copies assessed by qPCR using primers specific for bisulfite-converted marker regions for Treg cells and for GAPDH. These qPCR analyses were also performed using the bisulfite-converted normalization standard (Table 8, section 1). The efficiency of qPCR for Treg cells and GAPDH should be equal as the novel genomic, non-bisulfite converted plasmid standard (the substrate) contains an equimolar amount of Treg cell-specific and GAPDH-specific genomic copies. Therefore, assessed deviation of Treg copy numbers from GAPDH copy numbers corresponds to differences in assay effiCiencies.

Treg(TSDR) copy numbers=6760 vs. GAPDH copy numbers=6273,33

This deviation defines the cell-type assay-specific correction factor. E.g.:

Treg(TSDR)copy numbers/GAPDH copy numbers/100=6760/6273.33=1.077.

For Treg cells an assay correction factor of 1.1 (average, n=3) was assessed (Table 8, section 3). Correcting the relative amount of Treg cells by factor 1.1 results in an absolute amount of 2.05% Treg cells within the unknown blood sample WB01.

relative amount of Treg cells/specific assay-correction factor=absolute amount of Treg

2.25%/1.1=2.05% Treg cells

TABLE 8 Assessment of Treg-specific assay-correction factor using a bisulfite-unconverted nucleic acid molecule as a plasmid standard. qPCR1 (FOXP3 TSDR) Assay Run-ID: 115_genomSTD_NormalizationFactorTreg 1) qPCR for bisulfite-converted normalization standard: qPCR for TSDR bisulfite- qPCR for GAPDH bisulfite- converted normalization convered normalization standard standard copy numbers copy numbers Standards for Quantification normalization normalization Standard-ID Plasmid Units CP Value standard CP Value standard Standard-1 31250 units 23.18 31500.00 23.10 32766.67 Standard-2  6250 units 25.55 6150.00 25.49 6010.00 Standard-3  1250 units 27.86 1250.00 27.71 1243.33 Standard-4  250 units 30.20 249.00 29.91 260.00 Standard-5   50 units 32.86 53.00 32.78 44.13 Standard-6   30 units 34.05 31.80 33.36 32.70 2) qPCR on blood sample of unknow composition for assessment of relative amount of Treg cells using the bisulfite-converted normalization standard as given under 1): qPCR for TSDR bisulfite qPCR for GAPDH bisulfite converted DNA converted DNA Sample ID copy numbers copy numbers unknown acc. to acc. to relative blood normalization normalization amount stable sample gender CP Value standard (1) CP Value standard (1) Treg WB01 female 32.38 67.70 25.49 6026.67 2.25% 3) qPCR on genomic plasmid standard for assessment of Treg-specific correction factor qPCR for TSDR bisulfite qPCR for GAPDH bisulfite converted DNA converted DNA copy numbers copy numbers % stable Sample ID dilution acc. to acc. to Treg/GAPDH genomic genom. normalization normalization genomic standard standard CP Value standard (1) CP Value standard (1) plasmid units GP5000 1 25.41 6760.00 25.44 6273.33 107.76 GP1000 1:5  27.71 1380.00 27.75 1206.67 114.36 GP200 1:25 29.93 301.00 29.82 278.00 108.27 Mean: 110.13 Normalization Factor: 1.10 4) Correction of relative amount of Tregs using Treg-specific correction factor to obtain absolute amount of Treg cells Treg Treg relative Normalization absolute amount Factor amount 2.25% 1.1 2.05%

Example 7 Development of Cell-Specific qPCR Assay for Detection and Discrimination of Neutrophil Granulocytes Detecting Cell-Type Specific, Differential Bisulfite Convertibility:

DNA from the purified neutrophil granulocytes (neutrophils), monocytes, CD4+ cells CD8+ cells, B cells, NK-cells, and NKT cells was bisulfite-treated and bisulfite converted DNA analyzed at various CpG dinucleotide motifs. The inventors then compared the bisulfite convertibility (finding C as for Cytosine that was methylated in the original (genomic) sequence versus T for cytosine that was unmethylated in the original sequence) of these CpG dinucleotides (see Table 4, position 259).

Surprisingly, it was found that specific areas in the genomic region of lipocalin-2 were differentially methylated in neutrophil granulocytes compared to all other blood cell types tested. These areas were defined as discovery fragments, such as e.g. SEQ ID 517 for neutrophils (Table 4, position 259).

Validation of Bisulfite Convertibility:

Then, upon finding of the differential bisulfite convertibility, the inventors analyzed larger genomic regions by means of bisulfite sequencing. This latter procedure served for exploring and extending the discovered, differentially methylated areas and was conducted, for example with the differentially bisulfite converted discovery fragment, SEQ ID 517, within the gene lipocalin-2 as disclosed herein (see Table 4, SEQ ID 517 discovery fragment and 518 discriminative region of interest (ROI)).

Within the discriminative ROI defined as SEQ ID 518 a preferred region of interest including preferable CpG positions to be analyzed was identified (amplicon (AMP) 1730, see FIG. 2 and SEQ ID 685).

Development of Cell-Type Specific qPCR Assay:

In AMP 1730, a detailed analysis was performed in order to develop a highly specific qPCR assay based on the use of amplification primers and probes. Amplification primers (forward and reverse) for bisulfite converted neutrophils specific AMP 1730 as well as probes were designed and tested (data not shown).

In order to develop a particularly preferred “perfect” primer system for the assay, primers were developed that do not correspond 100% to the original bisulfite converted sequence but include specific mismatches that surprisingly increased the specificity. Mismatches in the primer sequence are underlined and bold.

TpG System (Detecting TpG Positions in Bisulfite-Converted DNA):

Forward Primer: q1730 nm2Fw2_M1:  ACCAAAAATACAACACTTCAA; Reverse Primer:  q1730 nm2R2:  GGTAATTGTTAGTAATTTTTGTG; Hydrolysis Probe: q1730 nm2P4:  FAM-CACTCTCCCCATCCCTCTATC-BHQ1.

CpG System (Detecting CpG Positions in Bisulfite-Converted DNA):

Forward Primer: q1730_m2F1:  TACCAAAAATACAACACTCCG Reverse Primer:  q1730_m2R2_M1:  AGGTAATTGTTAGTAATTTTTACG Hydrolysis Probe: q1730 m2P1:  HEX-CTCACTCTCCCCGTCCCTCTATC-BHQ1

The technical specificity of the TpG-specific PCR-system was tested based on test-templates (see FIG. 4). TpG and the CpG specific PCR system were found to be highly specific for the bisulfite converted and the non-bisulfite converted template, respectively. Additionally, the TpG-specific and CpG-specific PCR system show no cross reactivity with the CpG and the TpG templates, respectively (FIG. 4 shown for TpG-specific PCR system). In order to further increase specificity of the qPCR primer system, Mg2+ concentration was increased from 3.2 mM (usually applied) to 3.5 mM (see FIG. 4).

The biological specificity of the neutrophils-specific qPCR-system was tested using certain sorted cell fractions as well as using whole blood samples (see Table 9). The established qPCR assay was found to be highly specific for neutrophils.

TABLE 9 summarizes the results of the qPCR-analysis of sorted immune cells and whole blood samples. Shown are the CP-values for plasmid standards, for immune cell types and whole blood samples, each for the bisulfite converted, neutrophil-specific marker copies (TpG PCR-system) and the non-bisulfite converted, neutrophil-specific marker copies (CpG PCR-system) system. Based on the plasmid standard the corresponding copy numbers (plasmid copies) were calculated from the CP-value as measured. (NTC) no template control; (nGRC) neutrophil granulocytes. q1730* (nGRC) Assay Run-ID: UBq1730_b_BSCT-Valid. qPCR for bisulfite-converted normalization standard: qPCR for nGRC bisulfite-converted qPCR for nGRC non-bisulfite-converted Standards for Quantification normalization standard (TpG) normalization standard (CpG) Standard-ID Plasmid Units CP Value Plasmid Units CP Value Plasmid Units Standard-1 31250 units 23.5 30433.3 23.8 30766.7 Standard-2  6250 units 25.8 6340.0 26.2 6300.0 Standard-3  1250 units 28.2 1316.7 28.6 1240.0 Standard-4  250 units 30.6 257.7 30.9 256.0 Standard-5   50 units 32.8 62.2 33.1 60.5 Standard-6   30 units NTC NTC ND ND ND ND Analyzed Samples PCR-System specific to “TpG” PCR-System specific to “CpG” % nGRC Epionts-ID Cell Type CP Value Plasmid units CP Value Plasmid units ‘TpG”/“CpG” bGRAN06 Basophila 35.49 14.27 29.09 875.33 1.60 eGRAN09 Eosinophila 35.24 16.20 30.68 300.00 5.12 nGRAN02 Neutrophils 30.52 270.67 35.73 11.70 95.86 MOC28 Monocytes 35.72 12.93 29.85 525.00 2.40 THC14 T-helper cells 42.70 0.91 30.80 278.00 0.33 CTL16 Cyototox. T-cells 37.72 5.04 29.41 706.00 0.71 NKC_Pool NK Cells 36.95 7.03 29.34 740.33 0.94 NKT19 NK T-cells 38.35 3.85 30.37 369.67 1.03 BLC06 B-Lymphocytes 39.57 2.41 29.91 502.67 0.48 WBL51 Whole Blood 30.61 253.67 31.69 152.67 62.43 WBL55 Whole Blood 29.43 561.00 30.84 268.67 67.62 WBL57 Whole Blood 31.59 134.00 32.08 117.67 53.25 WBL58 Whole Blood 31.94 107.33 31.68 154.33 41.02

The relative amount of neutrophils in the sample is calculated from the number of bisulfite converted, neutrophil-specific marker copies and the sum of bisulfite converted and non-bisulfite converted neutrophil-specific marker copies in the sample as follows:

% neutrophils=no. of bisulfite converted neutrophil copies/no. of non-bisulfite converted neutrophil copies×100;

% neutrophils=253.67/(253.67+152.67)×100=62.43

The present assay is special in the sense that the amplification of the bisulfite-converted neutrophils-target-DNA using “common” fitted primers and standard PCR-protocols does not provide a sufficient result. Only after using amplification primers that were designed having a mutation (a “mismatch”) at strategic sites as identified herein, together with the use of a much higher Mg²⁺-concentration in the PCR allows for the efficient amplification of the neutrophils-target region.

In a next step a genomic plasmid standard can be designed and cell-specific assay-correction factor can be assessed (see Example 6).

Example 8 Assessment of Cell-Specific Assay-Correction Factor Using a Non-Bisulfite-Converted Nucleic Acid Molecule (Genomic Plasmid Standard) as Normalization Standard to Quantify Absolute Number of Cells Per Microliter

The inventors developed non-bisulfite converted, genomic-plasmid standards as a normalization standard. One of these genomic plasmid standards comprises a marker region being specific for T-lymphocytes as well as a marker region being cell-type unspecific (GAPDH, housekeeping gene, detecting all cells, 100% of cells). Each single plasmid contains the same number of copies of these two marker regions (equimolar); two of these plasmids correspond to the number of DNA copies per one single immune cell and are therefore counted as one single cell. A stock solution containing defined numbers of said genomic plasmid molecules is used to determine the T-lymphocyte-specific assay-correction factor as well as to assess the absolute number of T-lymphocytes per microliter within an unknown blood sample.

In a first step, DNA of four human blood samples of unknown composition was isolated. This isolated DNA as well as the genomic plasmids of genomic plasmid standard were bisulfite treated. Following, the amount of copies of bisulfite converted T-lymphocyte-specific and GAPDH-specific marker regions were assessed by qPCR (Table 10, section B, C). These qPCR analyses were performed using a bisulfite-converted normalization standard (Table 10, section A) indicating the relative number of bisulfite-converted DNA as well as relative number of genomic plasmid copies containing the T-lymphocyte-specific marker region and the GAPDH marker region (Table 10 section B, C).

The relative amount of T-lymphocytes in percent within unknown blood samples is calculated as number of bisulfite converted T-lymphocyte-specific marker copies related to bisulfite converted GAPDH copies (Table 10, section B).

${\% \mspace{14mu} T\text{-}{lymphocytes}} = \frac{\; \begin{matrix} {{{no}.\mspace{14mu} {bisulfite}}\text{-}{converted}\mspace{14mu} T\text{-}{lymphocyte}\text{-}{specific}} \\ {\; {{marker}\mspace{14mu} {copies} \times 100}} \end{matrix}\;}{{{no}.\mspace{14mu} {bisulfite}}\text{-}{converted}\mspace{14mu} {GAPDH}\mspace{14mu} {copies}}$   (e.g.  RD 260314):  1896.7/6570.0 × 100 = 28.87%  

In a next step, T-lymphocyte-specific assay-correction factor based on said genomic plasmid standard was assessed (Table GR, section C). As described above, said genomic plasmid standard was bisulfite converted and number of plasmid copies assessed by qPCR using primers specific for bisulfite-converted marker regions for T-lymphocytes and for GAPDH. These qPCR analyses were also performed using the bisulfite-converted normalization standard (Table 10, section A). The efficiency of qPCR for T-lymphocytes and GAPDH should be equal as the novel genomic, non-bisulfite converted plasmid standard contains an equimolar amount of copies T-lymphocyte-specific and GAPDH-specific marker regions. Therefore, assessed deviation of genomic T-lymphocyte copy numbers from GAPDH copy numbers corresponds to differences in qPCR assay efficiencies.

e.g. Mean T-lymphocyte copy numbers=6058 vs. mean GAPDH copy numbers=5483

This deviation defines the cell-type assay-specific correction factor.:

Mean T-lymphocytes copy numbers/GAPDH copy numbers=6058/5483=1.1.

For T-lymphocytes an assay correction factor of 1.1 (average, n=2) was assessed (Table 10, section C). Correcting the relative amount of T-lymphocytes by factor 1,1 results in an absolute amount, e.g., of 26.24% T-lymphocytes within the unknown blood sample RD260314 (Table 10, section D).

absolute amount of T-lymphocytes=relative amount of T-lymphocytes/specific assay-correction factor

e.g.:28.87%/1.1=26.24% Treg cells

Additionally, the absolute number of T-lymphocytes per microliter within unknown blood samples was assessed (Table 10, section E). As described above, said genomic plasmid standard (stock solution of 6250 copies per microliter) was bisulfite converted and number of plasmid copies assessed by qPCR using primers specific for bisulfite-converted marker region for T-lymphocytes (section C). These qPCR was performed using the bisulfite-converted normalization standard (section A).

The amount of T-lymphocytes per microliter within unknown blood samples is calculated from relation of known, initial number of genomic plasmids of stock solution (6250 copies) and qPCR assessed number of copies of T-lymphocyte-specific marker within unknown blood samples (see section B) to qPCR assessed number of copies of genomic plasmid standard (see section C).

${T\text{-}{lymphocytes}\text{/}{µl}} = \frac{\begin{matrix} {{{no}.\mspace{14mu} {plasmid}}\mspace{14mu} {copies}\text{/}{µl} \times} \\ {{{no}.\mspace{14mu} {bisulfite}}\text{-}{converted}\mspace{14mu} T\text{-}{lymphocyte}\text{-}{specific}} \end{matrix}}{{Mean}\mspace{14mu} {{no}.\mspace{14mu} {of}}\mspace{14mu} {qPCR}\mspace{14mu} {assessed}\mspace{14mu} {plasmid}\mspace{14mu} {copies} \times 2}$ (e.g.  RD 260314):  (6250 × 1896.7)/(6058.3 × 2) = 978  T-lymphocytes/µl

(See Table 10 below.)

TABLE 10 Assessment of Treg-specific assay-correction factor using a bisulfite-unconverted nucleic acid molecule as a plasmid standard. Assessment of absolute cell number in % as well as of cells per μl A) qPCR for bisulfite-converted normalization standard: qPCR for T-lymphocyte qPCR for GAPDH bisulfite-converted bisulfite-convered normalization standard normalization standard copy copy Standards for Quantification numbers numbers Standard- Plasmid CP normalization CP normalization ID Units Value standard Value standard Standard-1 31250 units 23.99 30500.00 23.30 31533.33 Standard-2  6250 units 26.22 6510.00 25.62 6263.33 Standard-3  1250 units 28.65 1223.33 27.93 1260.00 Standard-4  250 units 30.90 258.67 30.30 241.33 Standard-5   50 units 33.14 50.00 32.86 48.93 B) qPCR on blood sample of unknow composition for assessment of relative amount of T-Lymphocytes using the bisulfite-converted normalization standard as given under A): qPCR for T-lymphocyte-specific qPCR for GAPDH-specific bisulfite converted DNA bisulfite converted DNA Sample ID copy numbers copy numbers relative unknown acc. to acc. to amount T- blood CP normalization CP normalization lymphocytes sample Value standard (A) Value standard (A) (%) RD260314 28.01 1896.7 25.55 6570.0 28.87 BF260314 27.54 2626.7 24.72 11700.0 22.45 MK260314 27.49 2703.3 24.86 10566.7 25.58 LK260314 27.69 2363.3 24.85 10700.0 22.09 C) qPCR on genomic plasmid standard for assessment of T-Lymphocyte-specific correction factor qPCR for T-lymphocyte-specific qPCR for GAPDH-specific bisulfite converted DNA bisulfite converted DNA % T- copy numbers copy numbers lymphocytes/ Sample ID number acc. to acc. to GAPDH genomic plasmid copies CP normalization CP normalization genomic standard per microliter Value standard (A) Value standard (A) plasmid units gnomSTD_02 6250 26.47 5503.3 25.88 5213.3 106 gnomSTD_02 6250 26.20 6613.3 25.74 5753.3 115 Mean: 6058.3 Mean: 5483 Mean: 110 Normalization Factor: 1.1 D) Correction of relative amount of T-lymphocytes using assay-specific correction factor (C) to obtain absolute amount of T-Lymphocytes (in %) Sample ID T- unknown Relative lymphocytes blood amount T- Normalization absolute sample lymphocytes Factor amount RD260314 28.87 1.1 26.24% BF260314 22.45 1.1 20.41% MK260314 25.58 1.1 23.26% LK260314 22.09 1.1 20.08% E) Normalizing relative amount of T-lymphocyte to cell number per microliter using genomic plasmid standard copy numbers no. plasmid copies Sample ID of T-lymphocyte-specific per μl × no. copies T-I bcDNA unknown bisulfite converted DNA Mean qPCR assessed blood sample (see B) no. of plasmid copies × 2 RD260314 1896.7  978 T-Lympohcytes/μl BF260314 2626.7 1355 T-Lympohcytes/μl MK260314 2703.3 1394 T-Lympohcytes/μl LK260314 2363.3 1219 T-Lympohcytes/μl 

1. A method for producing an epigenetic haemogram, comprising the steps of epigenetically detecting blood cells in a biological sample, and quantifying said blood cells as detected using a normalization standard, wherein said normalization standard is a nucleic acid molecule comprising at least one marker-region being specific for each of the blood cells to be detected, and at least one control-region being cell-unspecific, wherein said regions are present in the same number of copies on said molecule and/or a natural blood cell sample of known composition.
 2. The method according to claim 1, wherein said normalization standard is a bisulfite-unconverted or bisulfite-converted nucleic acid molecule.
 3. The method according to claim 2, wherein said bisulfite-unconverted or bisulfite-converted nucleic acid molecule is selected from a plasmid, a yeast artificial chromosome (YAC), human artificial chromosome (HAC), P1-derived artificial chromosome (PAC), a bacterial artificial chromosome (BAC), and a PCR-product.
 4. The method according to claim 1, wherein said natural blood cell sample is a blood sample of known cellular composition, and/or of known composition of blood and immune cell types.
 5. The method according to claim 1, further comprising the step of correcting said epigenetic haemogram as produced with an assay specific correction factor.
 6. The method according to claim 1, further comprising the step of obtaining a comprehensive blood picture, based on said detecting and quantifying.
 7. The method according to claim 1, wherein cell-type marker regions are detected that discriminate a specific cell type and/or at least one specific subpopulation of cells from other cells of a leukocytogram, a T-lymphocytogram, a granulocytogram, a monocytogram, a B-lymphocytogram and/or a NK-cytogram.
 8. The method according to claim 1, wherein said at least one cell-unspecific control-region is selected from a gene expressed in all cells to be detected.
 9. The method according to claim 1, wherein said normalization standard is bisulfite-unconverted and contains at least one bisulfite-convertible CpG position.
 10. The method according to claim 1, wherein said quantifying of cell types in said biological sample is based on normalization of the relative amount of cell-type specific and unspecific chromatin using a bisulfite-unconverted normalization standard or using a bisulfate-converted normalization standard.
 11. The method according to claim 1, wherein said normalization using a bisulfite-unconverted normalization standard is indicative for an absolute amount and/or percentage of content of cells within said biological sample.
 12. The method according to claim 5, wherein said assay correction factor for each cell-type specific and unspecific assay is obtained by comparing the quantitative composition of said natural blood cell sample with the relative amount of bisulfite-convertible chromatin of said natural blood cell sample using the normalization standard.
 13. The method according to claim 5, wherein said correction of relative amount of cells within said biological sample is obtained by using the assay correction factor, and is indicative for the absolute amount and percentage of the content of cells within the biological sample.
 14. The method according to claim 1, wherein said biological sample is a sample of unknown cellular composition.
 15. The method according to claim 1, wherein said biological sample is selected from a mammalian body fluid.
 16. The method according to claim 1, wherein said epigenetic haemogram comprises a leukocytogram, and/or a T-lymphocytogram, and/or a granulocytogram, and/or a monocytogram, and/or a B-lymphocytogram, and/or a NK cytogram.
 17. The method according to claim 16, wherein a) said leukocytogram is selected from T-lymphocytes, natural killer cells, B-lymphocytes, monocytes, and/or granulocytes, and combinations thereof, b) said T-lymphocytogram is selected from CD3⁺CD4⁺, CD4⁺ memory, CD4⁺ effector cells, CD4⁺ naïve, CD3⁺CD8⁺, CD8⁺ memory, CD8⁺ effector cells, CD8⁺ naïve, CD3⁺CD8⁻CD4⁺, CD3⁺CD8⁺CD4⁺, NKT cells, iTreg, Treg, Tfh, Th1, Th2, TH9, Th17, Th19, Th21, Th22, memory and/or effector T helper cells, and combinations thereof, c) said granulocytogram is selected from basophilic, eosinophilic, neutrophilic-, overall neutrophil granulocytes, and/or granulocytic myeloid-derived suppressor cells, and combinations thereof, d) said monocytogram is selected from CD14⁺ monocytes, CD14⁻ monocytes, macrophages, plasmacytoid dendritic cells, monocytic myeloid-derived suppressor cells, intermediate monocytes, classical monocytes, non-classical monocytes, and/or overall dendritic cells, and combinations thereof, e) said B-lymphocytogram is selected from naïve B cells, pre B cells, memory B cells, transitional B cells and/or immature B cells, and combinations thereof, and f) said NK cytogram is selected from CD56^(dim) and/or CD56^(bright) NK cells.
 18. The method according to claim 1, wherein said at least one CpG position to be analyzed is present in a marker region in a 5′ region upstream from the transcription start, a promoter region, a 5′ or 3′ untranslated region, an intron, an exon/intron border, and/or in a 3′ region downstream of the transcriptional stop.
 19. The method according to claim 1, wherein a bisulfite conversion of at least one CpG position within any one of SEQ ID NOs:1 to 684 is indicative for a respective cell type as listed in table 4 or wherein a bisulfite conversion of at least one CpG position within any one of SEQ ID NO:685 or 686 is indicative for a neutrophilic granulocyte, or wherein a bisulfite conversion of at least one CpG position within any one of SEQ ID NOs:687 to 689 is indicative for an eosinophilic granulocyte.
 20. The method according to claim 1, further comprising the step of generating a knowledge base comprising information about the cell-specific assay-correction factors estimated during previous assessment of epigenetic haemograms.
 21. The method according to claim 1, wherein said determining the relative amount of bisulfite-convertible and/or non-bisulfite convertible DNA or nucleic acid comprises a method selected from specific enzymatic digests or dye exclusion technologies; bisulfite sequencing; next generation sequencing nanopore sequencing; single molecule real-time sequencing; analyses of epigenetic modifications in promoter regions; using primers specific for bisulfite-converted DNA; using blocking oligonucleotides specific for bisulfite-converted DNA; using fluorescence-labeled, quenched oligonucleotide probes; using primers for single nucleotide primer extension specific for bisulfite-converted DNA; digital or quantitative PCR analysis; and specific selective (nucleic acid and/or chromatin) precipitation.
 22. The method according to claim 1, further comprising the step of concluding on an immune status of a mammal based on said epigenetic haemogram.
 23. The method according to claim 1, further comprising the step of monitoring said cellular composition in said biological sample as identified by comparing said composition and/or haemogram with the composition in an earlier sample taken from the same mammal, and/or with the composition in a control sample.
 24. A method for diagnosing a disease or a predisposition for a disease or to assess the risk to develop a disease, comprising a method according to claim 1, and concluding on the disease or a predisposition for said disease based on the cellular composition in said biological sample as identified.
 25. A method for identifying the effect of a chemical or biological substance on the composition of cells, comprising performing the method according to claim 1 on a blood sample obtained from a mammal treated with said substance, and comparing the composition of cells in said sample with the composition in an untreated sample.
 26. A kit for producing an epigenetic haemogram, comprising materials for performing the method according to claim 1, optionally with instructions for use.
 27. (canceled) 